Cavalier King Charles Spaniels with Chiari-like malformation and Syringomyelia have increased variability of spatio-temporal gait characteristics

The Cavalier King Charles Spaniel (CKCS) is an example of a dog selectively bred for distinct conformational traits. The breed shows a high degree of juvenile behaviour and brachycephalic traits associated with a juvenile morphology (paedomorphic) when compared with the wolf and other companion dog breeds [1]. This selection for paedomorphism may have resulted in a specific morphology of the skull and brain, leading to a hereditary pathological mismatch between skull volume and brain volume, with a resulting herniation of part of the cerebellum and brainstem into or through the foramen magnum, a condition called Chiari-like Malformation (CM). Chiari-like malformation is linked to Syringomyelia (SM) which causes neuropathic pain [2]. CM is estimated to afflict up to 92% of the CKCS population [2]. It is believed that more than half of CKCS with CM will develop fluid-filled cavities within the spinal cord (SM) later in life and are affected with varying degrees of clinical signs. In fact, 25% of dogs with CM had SM at the age of 12 months increasing to 70% at 6 years of age [3]. In addition, the CKCS, when compared with other dogs, has a relatively larger cerebellum [2], which may predispose them to cerebellar dysfunction. The clinical signs of CM and SM include neck and head pain, cervical scoliosis, thoracic and pelvic limb ataxia (incoordination), thoracic limb paresis and neuropathic pain [4].

Coordination has been defined as “an ability to maintain a context-dependent and phase-dependent cyclical relationship between different body segments or joints in both spatial and temporal domains” [5]. Coordination of gait involves a complex interaction between proprioceptive receptors, stretch receptors in muscles, spinal cord, cerebellum, motor cortex and vision. If either of these pathways are diseased, such as in CM and SM in the CKCS, changes in the variation of gait are expected.

The cerebellum is known to adjust and control balance and locomotion, incorporating autonomous sensorimotor feedback from the spinal cord and feed-forward from the cerebral cortex and other primary and secondary motor centres of the brain [6]. The cerebellum also aids stabilisation of motor control [7] and inter-limb coordination [8]. Cerebellar ataxia is clinically characterised by dysmetria most commonly with hypermetria. Objective human gait analysis of patients with cerebellar ataxia show a) slower walk, prolonged duration of stance phase and increased variation of spatio-temporal characteristics and b) a wide based stance [9–11]. This increased variation of spatio-temporal characteristics is similar to that found in cats with experimentally induced spinal cord injury [12] and dogs with cervical spondylotic myelopathy [13]. We therefore hypothesised that CKCS diagnosed with CM or CM with SM, would have significantly increased a) variation of the spatio-temporal gait characteristics (stride length and duration of step cycle and stance) and b) wider base of support with an increased distance between pelvic and thoracic paws during walk. Because so many CKCS are affected and therefore cannot serve as controls and we therefore had to choose a control breed of similar weight and frame such as the Border Terriers, with no genetic predisposition for cerebellar or spinal cord disease. It should be mentioned that Border Terriers have been found to have paroxysmal movement disorders [14], and some puppies have been reported to have a leukoencephalomyelopathy [15] as well as a hypomyelination syndrome [16] where the latter two syndromes are present in young puppies.

A total of 25 dogs were recruited to the three groups with 9 dogs in group CM with a median age of 6 ranging from 3 years to 10 years, 8 dogs in group CMSM with a median age of 6.5 years ranging from 4 to 8 years. MRIs were performed on the CKCS dogs as they were enrolled in other studies or screened for breeding purposes. Additional file 1: Table S1 shows details of the clinical findings in the CKCS where none of the dogs in the CM group showed clinical signs and two of the CKCS in the SM group showed clinical signs of neuropathic pain with phantom scratching. Eight Border Terriers were recruited for the Control group with a median age of 5 years ranging from 8 months to 9 years. None of the CKCS or Border Terriers were on any medications.

Firstly, we demonstrate increased variability through a significant increase in CV for the spatio-temporal characteristics for the CM group and the CMSM group compared with the control breed (Table 2 - and illustrated in Fig. 1). In particular, we find an increased CV of the ipsilateral distance between paws and length of the stride for both the CM and CMSM groups. Secondly, we demonstrate that CKCS in group CMSM, compared to the control group, have a significantly wider base of support in the thoracic limbs but not in the pelvic limbs (Table 2).

Motor control theories such as the uncontrolled manifold hypothesis and synergies are the current prevailing theories for how quadrupeds and bipeds maintain a tight control of coordination. The uncontrolled manifold theory suggests that the extremities and head aim to keep the centre of mass (CoM) as stable as possible by varying the trajectory of the extremities [22]. In a recent study of able-bodied subject and stroke patients Papi et al. [23] investigated the uncontrolled manifold method for both CoM and extremities and found less variation of extremity kinematic trajectory over time after the stroke with and without an orthoses. The decreasing variability of CoM and extremities over time in the stroke subject suggest a relearning of gait. It is not known how different components of the peripheral and central nervous system contributes to learning of gait but it is known that the cerebellum plays a central role in fine-tuning of gait and early learning of gait and other motor tasks [6]. Cerebellar deficits or cranial cervical myelopathies are therefore obvious possible explanations for the increased variation of spatio-temporal characteristics in the CKCS with CM or CMSM in our study. Dogs with spinal cord injuries have impaired coordination between thoracic and pelvic limbs [24]. There may be breed differences resulting in small variations of stability of distal limb spatio-temporal characteristics however these are not thoroughly described in the literature.

Children and adult humans with cerebellar ataxia and normal children show increased gait variability [11, 25–27]. Increased step width and variability of gait parameters could therefore be a primitive stabilising mechanism for both spinal cord and cerebellum. When compared to the control group, dogs with CM and CMSM exhibited a wider distance between thoracic paws. Similarly dogs with cervical spondylomyelopathy have increased distance between their thoracic but not pelvic limbs [13] and thus a wider base of support using the thoracic limbs may be a stabilising mechanism adapted for both cerebellar disease and spinal cord disease however breed effects cannot be ruled out. Measurements of distance between the shoulder joints were obtained and there was no difference between the CKCS and the control group, which confirmed that this observation is due to the CM and CMSM groups adopting a wider base of support rather than a result of differences in breed conformation.

The increased variability of ipsilateral distance between paws and stride length in both the CM and CMSM groups is similar to that documented in humans with cerebellar ataxia [9] as well as dogs with spinal cord injury [28, 29]. Furthermore, the increased variability is suggestive of an incoordination between pelvic and thoracic limbs with hypermetria, an abnormality of gait often associated with dysfunction of the cerebellum [11] or cranial spinal cord injury [13, 24]. The increased variation in distance between ipsilateral paws at the time of ground contact for the CM group and the CMSM group is similar to that reported in ataxic dogs with thoracolumbar spinal cord disease during walk on a treadmill [30]. The increased variability of step cycle duration for the CM group when compared to the control group is compatible with findings in dogs with spinal cord injury [31]. In our study we could not demonstrate an effect of SM alone on gait parameters, but there was an effect of the changes associated with CM which could suggest an involvement of the cerebellum in CM and fine-tuning of gait. The lack of differences between the CM and CMSM groups may be associated with breed specific differences or disease affection of the spinocerebellar tracts however greater numbers are necessary to elucidate the details of subtle gait changes associated with neuro-localisations.

The human preference for juvenile traits in the CKCS pedigree has had a significant impact on behaviour [1] where the CKCS has a reduced repertoire of normal adult behaviour such as absence of submissive signals and reduced threat behaviour such as baring teeth [1, 32]. We know that the CKCS has cerebellar pathology and syringomyelia [2] and with our demonstration of altered gait, it could be argued that we appear to maintain the dogs in a “puppy like state” throughout their lives.

We conclude that Cavalier King Charles Spaniels with CM and CMSM have an increased variation of the ipsilateral distance between paws and length of the stride and a significantly wider base of support in the thoracic limbs but not in the pelvic limbs compared to Border Terriers. This could be an effect of cerebellar disease or cranial spinal cord disease however further breed-to-breed gait studies and objective quantification of hypermetria are necessary to further this conclusion. The increased spatial variation from CM and CMSM compared to control dogs could be used in rehabilitation and tracking of gait over time as well as monitoring for effect of treatment on gait changes and coordination.