Publications by authors named "Clare Rusbridge"

72 Publications

Clinical features, treatment and outcome of discospondylitis in cats.

J Feline Med Surg 2021 Jun 8:1098612X211020159. Epub 2021 Jun 8.

Dovecote Veterinary Hospital, Castle Donington, Derby, UK.

Objectives: There is a paucity of information on feline discospondylitis. This study aimed to describe the signalment, clinical and laboratory findings, aetiological agents, treatment and outcome in cats affected by discospondylitis.

Methods: This was a retrospective review of the medical records of cats diagnosed with discospondylitis at four referral institutions.

Results: A total of 17 cats were identified. Most were domestic shorthair cats (76.5%) and male (58.8%), with a median age of 9 years (range 0.9-14) and a median duration of clinical signs of 3 weeks (range 0.3-16). All cats presented with spinal hyperaesthesia; 3/17 had pyrexia. Neurological dysfunction was found in 64.7% of cats, which was indicative of a T3-L3 or L4-S2 spinal segment, associated nerve root or associated nerve neurolocalisation. Haematology, serum biochemistry and urinalysis revealed occasional inconsistent non-specific changes. All cats underwent urine culture; 9/17 cats also had a distinct tissue cultured. Positive bacterial cultures were obtained in two cats (11.8%) for species (urine, blood and intradiscal fine-needle aspirate) and (urine); both presented with multifocal discospondylitis. Treatment was non-surgical in all cats, with sustained antibiotic therapy for a median of 3 months (range 1-9). Analgesia provided included non-steroidal anti-inflammatory drugs, alone or in combination with gabapentin. Restricted exercise was advised for a minimum of 4 weeks. Outcome information available in 12 cats was excellent in terms of pain control and neurological function in 10 cats (83.3%) at the time of stopping antibiotics. Recurrence occurred in one case, which had received a single antibiotic for 6 weeks, and relapsed 4 months after presentation. One other case failed to improve and was euthanased during the course of hospitalisation.

Conclusions And Relevance: Feline discospondylitis is uncommon and no obvious signalment predisposition was found in this study. Spinal hyperaesthesia was universally present, with neurological dysfunction also highly prevalent. Bacterial culture was unrewarding in most cases. Amoxicillin-clavulanic acid or cephalosporins are reasonable choices for first-line antibiotics. Prognosis was favourable, with no long-term evidence of recurrence in cats on sustained antibiotic therapy, for a mean duration of 3 months.
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http://dx.doi.org/10.1177/1098612X211020159DOI Listing
June 2021

Persistent fontanelles in Chihuahuas. Part I. Distribution and clinical relevance.

J Vet Intern Med 2021 Jul 24;35(4):1834-1847. Epub 2021 May 24.

Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.

Background: The Chihuahua dog breed is known for frequent occurrence of a bregmatic fontanelle on the dorsal skull. A common conception is that this skull defect is a clinically irrelevant finding. No studies, however, describe its prevalence or whether it is accompanied by other persistent fontanelles (PFs). Although Chihuahuas are predisposed to Chiari-like malformation (CM) and syringomyelia (SM), it is unknown whether PFs occur more commonly in dogs with clinical signs that are caused by CM or SM.

Hypothesis/objectives: To describe the number and location of PFs at cranial sutures (CSs) and to compare the occurrence of these PFs in dogs with and without CM/SM-related clinical signs. We hypothesized that PFs also occur commonly at lateral and caudal cranial surfaces, affect a higher number of CSs, and are larger in dogs with CM/SM-related clinical signs.

Animals: Fifty client-owned Chihuahuas with or without CM/SM-related clinical signs.

Results: Of the 50 dogs evaluated, 46 (92%) had either 1 or several PFs. The mean ± SD number of PFs was 2.8 ± 3.0 (range, 0-13). A total of 138 PFs occupied 118 CSs with 57 (48%) located dorsally, 44 (37%) caudally, and 17 (14%) laterally. The number of CSs affected by PFs was significantly higher (P ≤ .001) and total PF area was significantly larger (P = .003) in dogs with CM/SM-related clinical signs.

Conclusions And Clinical Importance: Persistent fontanelles are very common in this group of Chihuahuas and appear at dorsal, lateral, and caudal cranial surfaces. They are more numerous and larger in Chihuahuas with CM/SM-related clinical signs.
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http://dx.doi.org/10.1111/jvim.16151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295709PMC
July 2021

Persistent fontanelles in Chihuahuas. Part II: Association with craniocervical junction abnormalities, syringomyelia, and ventricular volume.

J Vet Intern Med 2021 Jul 3;35(4):1848-1856. Epub 2021 May 3.

Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.

Background: Persistent fontanelles (PFs) are, in Chihuahuas, almost ubiquitous. Furthermore, Chihuahuas are predisposed to other craniomorphological abnormalities, including syringomyelia (SM), ventriculomegaly, and craniocervical junction (CCJ) overcrowding resulting in neural tissue deviation. It is, however, undetermined if PFs are more common in dogs with these structural abnormalities, and their etiology is unknown.

Hypothesis/objectives: Persistent fontanelles are more numerous and larger in Chihuahuas with low body weight, older age, SM, dilated fourth ventricle, ventriculomegaly, and CCJ overcrowding.

Animals: Fifty client-owned Chihuahuas.

Methods: Cross-sectional study evaluating the association of both the number of cranial sutures affected by PFs (NAS) and total fontanelle area (TFA), based on computed tomography with SM, fourth ventricle dilatation, lateral ventricle volume, and extent of neural tissue compression at the CCJ based on magnetic resonance images.

Results: The NASs was higher and TFA larger in dogs with low body weight (NAS: P = .007; 95% confidence interval [CI] = 0.384-0.861; TFA: P = .002; 95% CI = -1.91 to -0.478), larger lateral ventricles (NAS: P ≤ .001; 95% CI = 1.04-1.15; TFA: P ≤ .001; 95% CI = 0.099-0.363), and more severe neural tissue compression at the CCJ (NAS: P ≤ .001; 95% CI = 1.26-2.06; TFA: P = .03; 95% CI = 0.066-1.13). Similarly, dogs with SM (NAS: P = .004; 95% CI = 1.26-3.32; TFA: mean ± SD, 130 ± 217 mm ; P = .05) had higher NAS and larger TFA than did dogs without SM (43.7 ± 61.0 mm ). Age was not associated with NAS (P = .81; 95% CI = 0.989-1.01) or TFA (P = .33; 95% CI = -0.269 to 0.092).

Conclusions And Clinical Importance: Persistent fontanelles are associated with small size, SM, ventriculomegaly, and CCJ overcrowding.
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http://dx.doi.org/10.1111/jvim.16123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295681PMC
July 2021

Comparison of volume of the forebrain, subarachnoid space and lateral ventricles between dogs with idiopathic epilepsy and controls using a stereological approach: Cavalieri's principle.

Canine Med Genet 2021 Mar 10;8(1). Epub 2021 Mar 10.

Present Address: University College London, Division of Surgery & Interventional Science, Aspire CREATe, Royal National Orthopaedic Hospital, Brockley Hill, Stanmore, Middlesex, HA7 4LP, UK.

Background: Canine idiopathic epilepsy (IE) is the most common chronic neurological brain disease in dogs, yet it can only be diagnosed by exclusion of all other potential causes. In people, epilepsy has been associated with a reduction in brain volume. The objective was to estimate the volume of the forebrain (FB), subarachnoid space (SAS) and lateral ventricles (LV) in dogs with IE compared to controls using Cavalieri's principle. MRI scans of case and control dogs were identified from two neurology referral hospital databases. Eight breeds with increased odds of having IE were included: Golden Retriever, Labrador Retriever, Cocker Spaniel, Border terrier, German Shepherd dog, Parson Jack Russell terrier, Boxer, and Border Collie. Five dogs of each breed with IE and up to five controls were systematically and uniformly randomly sampled (SURS). The volume of the FB, SAS and LV were estimated from MRI scans by one blinded observer using Cavalieri's principle.

Results: One hundred-two dogs were identified; 56 were diagnosed with IE and 46 were controls. There was no statistically significant difference in FB, SAS and LV volume between dogs with IE and controls. Dogs with a history of status epilepticus had significantly larger FB than those without (p = 0.05). There was a border-line trend for LV volume to increase with increasing length of seizure history in the IE group (p = 0.055).

Conclusion: The volumes of the FB, SAS and LV are not different between dogs with IE and controls, so IE remains a diagnosis of exclusion with no specific neuroanatomical biomarkers identified. This is the first time FB and SAS volume has been compared in dogs with IE. Unfortunately, we have shown that the results reporting significantly larger FBs in dogs with status epilepticus and LV volume increase with length of seizure history were likely confounded by breed and should be interpreted cautiously. Whilst these associations are interesting and clinically relevant, further investigation with breed-specific or larger, breed-diverse populations are required to permit strong conclusions. The Cavalieri principle provided an effective estimation of FB, SAS and LV volumes on MRI, but may be too time-intensive for use in clinical practice.
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http://dx.doi.org/10.1186/s40575-021-00101-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944915PMC
March 2021

The Need for Head Space: Brachycephaly and Cerebrospinal Fluid Disorders.

Life (Basel) 2021 Feb 12;11(2). Epub 2021 Feb 12.

Faculty of Health & Medical Sciences, School of Veterinary Medicine, University of Surrey, Guildford GU2 7AL, UK.

Brachycephalic dogs remain popular, despite the knowledge that this head conformation is associated with health problems, including airway compromise, ocular disorders, neurological disease, and other co-morbidities. There is increasing evidence that brachycephaly disrupts cerebrospinal fluid movement and absorption, predisposing ventriculomegaly, hydrocephalus, quadrigeminal cistern expansion, Chiari-like malformation, and syringomyelia. In this review, we focus on cerebrospinal fluid physiology and how this is impacted by brachycephaly, airorhynchy, and associated craniosynostosis.
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http://dx.doi.org/10.3390/life11020139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918167PMC
February 2021

Syringopleural shunt placement in a pug with a cervical spinal diverticulum and associated syringomyelia.

Clin Case Rep 2020 Jul 13;8(7):1142-1148. Epub 2020 Apr 13.

School of Veterinary Medicine Guildford UK.

We report persistence of associated syringomyelia and formation of newly caudal spinal arachnoid diverticulum, following marsupialization surgery. We describe syringopleural shunt placement as a novel approach to treat both conditions in a Pug dog.
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http://dx.doi.org/10.1002/ccr3.2845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364096PMC
July 2020

Neurobehavioral Disorders: The Corticolimbic System in Health and Disease.

Authors:
Clare Rusbridge

Vet Clin North Am Small Anim Pract 2020 Sep 14;50(5):1157-1181. Epub 2020 Jul 14.

Fitzpatrick Referrals, Godalming, Surrey GU7 2QQ, UK; School of Veterinary Medicine, Faculty of Health & Medical Sciences, University of Surrey, Guildford, Surrey GU2 7AL, UK. Electronic address:

The corticolimbic system (prefrontal cortices, amygdala, and hippocampus) integrates emotion with cognition and produces a behavioral output that is flexible based on the environmental circumstances. It also modulates pain, being implicated in pathophysiology of maladaptive pain. Because of the anatomic and function overlap between corticolimbic circuitry for pain and emotion, the pathophysiology for maladaptive pain conditions is extremely complex. Addressing environmental needs and underlying triggers is more important than pharmacotherapy when dealing with feline orofacial pain syndrome or feline hyperesthesia syndrome. By contrast, autoimmune limbic encephalitis requires prompt diagnosis and management with immunosuppression and seizure control.
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http://dx.doi.org/10.1016/j.cvsm.2020.06.009DOI Listing
September 2020

Limited dorsal myeloschisis in three cats: a distinctive form of neural tube defect.

JFMS Open Rep 2020 Jan-Jun;6(1):2055116920924307. Epub 2020 Jun 29.

Fitzpatrick Referrals Orthopaedics and Neurology, Eashing, UK.

Case Series Summary: The aim of this case series was to describe the clinical presentation, imaging findings and histopathology of three cats with limited dorsal myeloschisis (LDM). The history, examination and MRI sequences were reviewed in three cases presented to a single referral hospital. The surgery report and histopathology were described in two cases. All cats were young (10 weeks old, 5 months old, 4 years old), presenting with varying degrees of progressive paraparesis. All had a midline skin defect overlying the spinal column that was either sunken or saccular, containing fluid thought to be cerebrospinal fluid. MRI sequences demonstrated tissue extending from the dura through an overlying bifid spinous process and attached to the dermis, with associated spinal cord tethering, atrophy and syringomyelia. Lesions were located at L2-L3, T8-T9 and L4. Histopathology described a fibroneural stalk with a glio-ependymal lining, surrounded by glial nests and nerve fibres. The youngest and most severely affected was euthanased, while the other two underwent surgery. Both regained independent ambulation with persistent paraparesis; however, one required ongoing management of urinary incontinence.

Relevance And Novel Information: LDM is a primary neural tube defect that may result in neurological deficits, including bladder dysfunction, and is characterised by a fibroneural stalk between the dermis and the spinal cord. Distinct MRI features, such as a visible intrathecal tract, dorsally tethered cord and syringomyelia, help distinguish this condition from the clinically similar dermoid sinus. The presence of progressive neurological signs, with a palpable midline defect overlying the affected spinal cord segment, may raise suspicion for this clinical entity in veterinary patients.
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http://dx.doi.org/10.1177/2055116920924307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328493PMC
June 2020

Brain gyrification in wild and domestic canids: Has domestication changed the gyrification index in domestic dogs?

J Comp Neurol 2020 12 20;528(18):3209-3228. Epub 2020 Jul 20.

Department of Anatomy, Des Moines University, Des Moines, Iowa, USA.

Over the last 15 years, research on canid cognition has revealed that domestic dogs possess a surprising array of complex sociocognitive skills pointing to the possibility that the domestication process might have uniquely altered their brains; however, we know very little about how evolutionary processes (natural or artificial) might have modified underlying neural structure to support species-specific behaviors. Evaluating the degree of cortical folding (i.e., gyrification) within canids may prove useful, as this parameter is linked to functional variation of the cerebral cortex. Using quantitative magnetic resonance imaging to investigate the impact of domestication on the canine cortical surface, we compared the gyrification index (GI) in 19 carnivore species, including six wild canid and 13 domestic dog individuals. We also explored correlations between global and local GI with brain mass, cortical thickness, white and gray matter volume and surface area. Our results indicated that GI values for domestic dogs are largely consistent with what would be expected for a canid of their given brain mass, although more variable than that observed in wild canids. We also found that GI in canids is positively correlated with cortical surface area, cortical thickness and total cortical gray matter volumes. While we found no evidence of global differences in GI between domestic and wild canids, certain regional differences in gyrification were observed.
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http://dx.doi.org/10.1002/cne.24972DOI Listing
December 2020

Facial changes related to brachycephaly in Cavalier King Charles Spaniels with Chiari-like malformation associated pain and secondary syringomyelia.

J Vet Intern Med 2020 Jan 5;34(1):237-246. Epub 2019 Nov 5.

School of Veterinary Medicine, Faculty of Health & Medical Sciences, Daphne Jackson Road, Guildford, Surrey, GU7 Q22, United Kingdom.

Background: Recent studies including an innovative machine learning technique indicated Chiari-like malformation (CM) is influenced by brachycephalic features.

Objectives: Morphometric analysis of facial anatomy and dysmorphia in CM-associated pain (CM-P) and syringomyelia (SM) in the Cavalier King Charles Spaniel (CKCS).

Animals: Sixty-six client-owned CKCS.

Methods: Retrospective study of anonymized T2W sagittal magnetic resonance imaging of 3 clinical groups: (1) 11 without central canal dilation (ccd) or SM (CM-N), (2) 15 with CM-P with no SM or <2 mm ccd (CM-P), and (3) 40 with syrinx width ≥4 mm (SM-S). Morphometric analysis assessed rostral skull flattening and position of the hard and soft palate relative to the cranial base in each clinical group and compared CKCS with and without SM-S.

Results: Sixteen of 28 measured variables were associated to SM-S compared to CM-N and CM-P. Of these 6 were common to both groups. Predictive variables determined by discriminant analysis were (1) the ratio of cranial height with cranial length (P < .001 between SM-S and CM-N) and (2) the distance between the cerebrum and the frontal bone (P < .001 between SM-S and CM-P). CM-P had the lowest mean height of the maxillary area.

Conclusions And Clinical Importance: CKCS with CM-P and SM-S have cranial brachycephaly with osseous insufficiency in the skull with rostral flattening and increased proximity of the hard and soft palate to the cranial base. Changes are greatest with CM-P. These findings have relevance for understanding disease pathogenesis and for selection of head conformation for breeding purposes.
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http://dx.doi.org/10.1111/jvim.15632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6979263PMC
January 2020

Behavioural changes in dogs with idiopathic epilepsy.

Vet Rec 2020 Jan 25;186(3):93. Epub 2019 Sep 25.

Clinical Sciences and Services, Royal Veterinary College, Hertfordshire, Hatfield, UK.

Background: Breed-specific and broader cohort studies have shown behavioural changes in dogs following the onset of idiopathic epilepsy (IE).

Methods: A cross-sectional, case-control questionnaire study was carried out to strengthen this body of evidence. Owners of eight breeds of dog completed an online questionnaire about their dogs' behaviour; once for control dogs and twice for dogs with IE, for both pre-IE and post-IE onset behaviour.

Results: Ninety-six (24.74 per cent) dogs with IE and 292 (75.26 per cent) age and breed-matched control dogs met the inclusion criteria. Control dogs had significantly higher 'Trainability' scores than dogs with IE (P=0.04). After IE, dogs had significantly higher 'Dog-Directed Fear or Aggression' (P=0.02), 'Non-Social Fear' (P=0.01), 'Attachment/Attention-Seeking Behaviour' (P=0.04), 'Attention-Deficit' (P=0.02) and significantly lower 'Trainability' (P=0.02) than prior to the onset of IE. Medication status did not significantly affect any behavioural factor, but drug-resistant dogs had significantly less 'Trainability' than drug-responsive (P=0.04) and partially drug-responsive dogs (P=0.03).

Conclusion: Behavioural differences related to cognitive function are seen between dogs with IE and controls. Behavioural changes related to anxiety, attention and cognition are seen in dogs following the onset of IE. The ability to clinically define and diagnose behavioural comorbidities in dogs is much needed from both a clinical and research perspective.
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http://dx.doi.org/10.1136/vr.105222DOI Listing
January 2020

Using machine learning to understand neuromorphological change and image-based biomarker identification in Cavalier King Charles Spaniels with Chiari-like malformation-associated pain and syringomyelia.

J Vet Intern Med 2019 Nov 24;33(6):2665-2674. Epub 2019 Sep 24.

CVSSP, Centre for Vision, Speech and Signal Processing, University of Surrey, Guildford, United Kingdom.

Background: Chiari-like malformation (CM) is a complex malformation of the skull and cranial cervical vertebrae that potentially results in pain and secondary syringomyelia (SM). Chiari-like malformation-associated pain (CM-P) can be challenging to diagnose. We propose a machine learning approach to characterize morphological changes in dogs that may or may not be apparent to human observers. This data-driven approach can remove potential bias (or blindness) that may be produced by a hypothesis-driven expert observer approach.

Hypothesis/objectives: To understand neuromorphological change and to identify image-based biomarkers in dogs with CM-P and symptomatic SM (SM-S) using a novel machine learning approach, with the aim of increasing the understanding of these disorders.

Animals: Thirty-two client-owned Cavalier King Charles Spaniels (CKCSs; 11 controls, 10 CM-P, 11 SM-S).

Methods: Retrospective study using T2-weighted midsagittal Digital Imaging and Communications in Medicine (DICOM) anonymized images, which then were mapped to images of an average clinically normal CKCS reference using Demons image registration. Key deformation features were automatically selected from the resulting deformation maps. A kernelized support vector machine was used for classifying characteristic localized changes in morphology.

Results: Candidate biomarkers were identified with receiver operating characteristic curves with area under the curve (AUC) of 0.78 (sensitivity 82%; specificity 69%) for the CM-P biomarkers collectively and an AUC of 0.82 (sensitivity, 93%; specificity, 67%) for the SM-S biomarkers, collectively.

Conclusions And Clinical Importance: Machine learning techniques can assist CM/SM diagnosis and facilitate understanding of abnormal morphology location with the potential to be applied to a variety of breeds and conformational diseases.
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http://dx.doi.org/10.1111/jvim.15621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6872629PMC
November 2019

Behavioral and clinical signs of Chiari-like malformation-associated pain and syringomyelia in Cavalier King Charles spaniels.

J Vet Intern Med 2019 Sep 9;33(5):2138-2150. Epub 2019 Jul 9.

School of Veterinary Medicine, Faculty of Health & Medical Sciences, University of Surrey, Surrey, United Kingdom.

Background: Diagnosis of Chiari-like malformation-associated pain (CM-P) or clinically relevant syringomyelia (SM) is challenging. We sought to determine common signs.

Animals: One hundred thirty client-owned Cavalier King Charles spaniels with neuroaxis magnetic resonance imaging (MRI) and diagnosis of CM-P/SM. Dogs with comorbidities causing similar signs were excluded with exception of otitis media with effusion (OME).

Methods: Retrospective study of medical records relating signalment, signs, and MRI findings. Dogs were grouped by SM maximum transverse diameter (1 = no SM; 2 = 0.5-1.99 mm; 3 = 2-3.9 mm: 4 = ≥4 mm). Differences between all groups-groups 1 versus 2-4 and groups 1-3 versus 4-were investigated. Continuous variables were analyzed using 2-sample t-tests and analysis of variance. Associations between categorical variables were analyzed using Fisher's exact or chi-square tests.

Results: Common signs were vocalization (65.4%), spinal pain (54.6%), reduced activity (37.7%), reduced stairs/jumping ability (35.4%), touch aversion (30.0%), altered emotional state (28.5%), and sleep disturbance (22%). Head scratching/rubbing (28.5%) was inversely associated with syrinx size (P = .005), less common in group 4 (P = .003), and not associated with OME (P = .977). Phantom scratching, scoliosis, weakness, and postural deficits were only seen in group 4 (SM ≥4 mm; P = .004).

Conclusions And Clinical Importance: Signs of pain are common in CM/SM but are not SM-dependent, suggesting (not proving) CM-P causality. Wide (≥4 mm) SM is associated with signs of myelopathy and, if the dorsal horn is involved, phantom scratching (ipsilateral) and torticollis (shoulder deviated ipsilateral; head tilt contralateral).
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http://dx.doi.org/10.1111/jvim.15552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766577PMC
September 2019

Magnetic resonance image findings in pug dogs with thoracolumbar myelopathy and concurrent caudal articular process dysplasia.

BMC Vet Res 2019 May 31;15(1):182. Epub 2019 May 31.

Fitzpatrick Referrals Ltd, Eashing, Godalming, Surrey, GU7 2QQ, UK.

Background: A retrospective case series study was undertaken to describe the magnetic resonance imaging (MRI) findings in Pug dogs with thoracolumbar myelopathy and concurrent caudal articular process (CAP) dysplasia. Electronic clinical records were searched for Pug dogs who underwent MRI for the investigation of a T3-L3 spinal cord segment disease with subsequent confirmation of CAP dysplasia with computed tomography between January 2013 and June 2017. Clinical parameters age, gender, neuter status, body weight, urinary or faecal incontinence, severity and duration of clinical signs were recorded. MRI abnormalities were described. Univariable non-parametric tests investigated the association between the clinical parameters and evidence of extra- or intra-dural spinal cord compression on MRI.

Results: 18 Pug dogs were included. The median age was 106 months with median duration of clinical signs 5 months. All presented with variable severity of spastic paraparesis and ataxia; 50% suffered urinary/faecal incontinence. In all cases, MRI revealed a focal increase in T2-weighted signal intensity within the spinal cord at an intervertebral level where bilateral CAP dysplasia was present; this was bilateral aplasia in all but one case, which had one aplastic and one severely hypoplastic CAP. MRI lesions were associated with spinal cord compression in all but one case; intervertebral disc protrusion resulted in extra-dural compression in 10 (56%) cases; intra-dural compression was associated with a suspected arachnoid diverticulum in 4 (22%) cases and suspected pia-arachnoid fibrosis in 3 cases (17%). There was no association between clinical parameters and a diagnosis of intra-dural vs extra-dural compression. CAP dysplasia occurred at multiple levels in the T10-13 region with bilateral aplasia at T11-12 most often associated with corresponding spinal cord lesions on MRI.

Conclusions: All Pugs dogs in this study were presented for chronic progressive ambulatory paraparesis; incontinence was commonly reported. Although intervertebral disc disease was the most common radiologic diagnosis, intra-dural compression associated with arachnoid diverticulae/fibrosis was also common. Bilateral CAP aplasia was present in all but one Pug dog at the level of MRI detectable spinal cord lesions. A causal relationship between CAP dysplasia and causes of thoracolumbar myelopathy is speculated but is not confirmed by this study.
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http://dx.doi.org/10.1186/s12917-019-1866-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544997PMC
May 2019

Cervical vertebral malformations in 9 dogs: radiological findings, treatment options and outcomes.

Ir Vet J 2019 23;72. Epub 2019 Apr 23.

Fitzpatrick Referrals, Halfway Lane, Eashing, Godalming, GU7 2QQ UK.

Background: Disregarding atlantoaxial instability in toy breed dogs associated with dens malformation and cervical spondylomyelopathy; cervical vertebral malformations are rare and poorly characterised in veterinary medicine and consequently treatment strategies and clinical outcome are sparsely documented.

Results: Electronic clinical records at our veterinary referral hospital between April 2009 and November 2018 were searched for patients presented with cervical myelopathy secondary to an underlying suspected vertebral malformation/instability. Nine dogs met the inclusion criteria. Two dogs were diagnosed with atlantoaxial pseudoarthrosis, two dogs with a syndrome similar to Klippel-Feil in humans, two dogs with congenital cervical fusion, two dogs with congenital C2-C3 canal stenosis and deficiencies of the dorsal arch of the atlas and laminae of the axis and one with axial rotatory displacement. Tetraparesis, proprioceptive deficits, cervical hyperesthesia and cervical scoliosis were the most common clinical signs. The axis was the most commonly affected vertebrae (8/9 patients). Patients diagnosed with Klippel-Feil-like Syndrome were the younger (average of 262.5 days) and patients diagnosed with fused vertebrae the oldest (average of 2896 days) in our studied population (average of 1580.8 days).

Conclusion: Cervical vertebral malformations are rare, or alternatively, being underdiagnosed in veterinary medicine. Patients diagnosed with Klippel-Feil-like Syndrome had a successful medium and long-term outcome with conservative management. Surgical treatment was often indicated for the other conditions presented in this study due to spinal instability and/or myelopathy. Stabilisations via ventral approaches were revealed to be safe. Multicentre and prospective studies are necessary in veterinary medicine to better characterise clinical outcomes in cervical vertebral malformations.
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http://dx.doi.org/10.1186/s13620-019-0141-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6480486PMC
April 2019

Pilot study of head conformation changes over time in the Cavalier King Charles spaniel breed.

Vet Rec 2019 01 11;184(4):122. Epub 2019 Jan 11.

Faculty of Health and Medical Sciences, School of Veterinary Medicine, University of Surrey, Guildford, UK.

Modern interpretation of head conformation in the Cavalier King Charles spaniel (CKCS) has favoured a smaller, more exaggerated, brachycephalic type than originally described in the 1929 breed standard. Recent research studies identified brachycephaly and reduced hind cranium as two conformational (dysmorphic) features that increase risk for symptomatic Chiari-like malformation and secondary syringomyelia (SM). A prospective pilot study investigated the hypothesis that dysmorphic head features could be assessed visually and correlated with risk of SM. Thirteen CKCS, selected from anonymised photographic evidence, were physically appraised by authorised Kennel Club judges using a head shape checklist. These subjective evaluations were then matched with objective measurements of the cranium (cephalic index and rostrocaudal doming) and their subsequent MRI. A positive correlation (P=0.039) between the judges' checklist score and rostrocaudal doming (hindskull ratio) and a positive correlation between the cephalic index and hindskull ratio (P=0.042) were identified. Five CKCS had no SM and their status tallied with 62 per cent of the judges' evaluation. Although the ability of adjudicators to identify differences in head conformation varied, there was sufficient association between the dysmorphic parameters and the risk of SM to cause concern and propose a larger study in CKCS breed.
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http://dx.doi.org/10.1136/vr.105135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589453PMC
January 2019

Clinical Application of Diagnostic Imaging of Chiari-Like Malformation and Syringomyelia.

Front Vet Sci 2018 28;5:280. Epub 2018 Nov 28.

School of Veterinary Medicine, Faculty of Health & Medical Sciences, University of Surrey, Guildford, United Kingdom.

Chiari-like malformation (CM) and syringomyelia (SM) is a frequent diagnosis in predisposed brachycephalic toy breeds since increased availability of MRI. However, the relevance of that MRI diagnosis has been questioned as CM, defined as identification of a cerebellar herniation, is ubiquitous in some breeds and SM can be asymptomatic. This article reviews the current knowledge of neuroanatomical changes in symptomatic CM and SM and diagnostic imaging modalities used for the clinical diagnosis of CM-pain or myelopathy related to SM. Although often compared to Chiari type I malformation in humans, canine CM-pain and SM is more comparable to complex craniosynostosis syndromes (i.e., premature fusion of multiple skull sutures) characterized by a short skull (cranial) base, rostrotentorial crowding with rostral forebrain flattening, small, and ventrally orientated olfactory bulbs, displacement of the neural tissue to give increased height of the cranium and further reduction of the functional caudotentorial space with hindbrain herniation. MRI may further reveal changes suggesting raised intracranial pressure such as loss of sulci definition in conjunction with ventriculomegaly. In addition to these brachycephalic changes, dogs with SM are more likely to have craniocervical junction abnormalities including rostral displacement of the axis and atlas with increased odontoid angulation causing craniospinal junction deformation and medulla oblongata elevation. Symptomatic SM is diagnosed on the basis of signs of myelopathy and presence of a large syrinx that is consistent with the neuro-localization. The imaging protocol should establish the longitudinal and transverse extent of the spinal cord involvement by the syrinx. Phantom scratching and cervicotorticollis are associated with large mid-cervical syringes that extend to the superficial dorsal horn. If the cause of CSF channel disruption and syringomyelia is not revealed by anatomical MRI then other imaging modalities may be appropriate with radiography or CT for any associated vertebral abnormalities.
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http://dx.doi.org/10.3389/fvets.2018.00280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279941PMC
November 2018

Two mixed breed dogs with sensory neuropathy are homozygous for an inversion disrupting FAM134B previously identified in Border Collies.

J Vet Intern Med 2018 Nov 11;32(6):2082-2087. Epub 2018 Oct 11.

Small Animal Hospital, School of Veterinary Medicine, University of Glasgow, Glasgow, United Kingdom.

Two unrelated 8-month-old male mixed breed dogs were presented for evaluation of progressive ataxia, knuckling, and lack of pain perception in the distal limbs. Because of the similarity in age of onset, progression, and clinical findings with previously described sensory neuropathy in Border Collies, the affected dogs were screened for an FAM134B mutation and were determined to be homozygous for the mutation. Despite few phenotypic similarities with other breeds, genetic testing for specific diseases should be considered in mixed breed dogs with compatible clinical signs, especially if ancestry is unknown.
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http://dx.doi.org/10.1111/jvim.15312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6272042PMC
November 2018

Morphogenesis of Canine Chiari Malformation and Secondary Syringomyelia: Disorders of Cerebrospinal Fluid Circulation.

Front Vet Sci 2018 27;5:171. Epub 2018 Jul 27.

Department of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom.

Chiari-like Malformation (CM) and secondary syringomyelia (SM), as well as their analogous human conditions, is a complex developmental condition associated with pain and accompanying welfare concerns. CM/SM is diagnosed ever more frequently, thanks in part to the increased availability of magnetic resonance imaging in veterinary medicine. Research over the last two decades has focused primarily on its pathophysiology relating to overcrowding of the cranial caudal fossa. More recent characterizations of CM/SM include brachycephaly with osseous reduction and neural parenchymal displacement involving the entire brain and craniocervical junction to include rostral flattening, olfactory bulb rotation, increased height of the cranium, reduced cranial base with spheno-occipital synchondrosis angulation, reduced supraoccipital and interparietal crest and rostral displacement of the axis and atlas with increased odontoid angulation. The most shared manifestation of CM is the development of fluid-filled pockets (syrinx, syringes) in the spinal cord that can be readily quantified. Dogs with symptomatic CM without SM have a reduced basioccipital bone, compensatory increased cranial fossa height with displaced parenchyma whereby the cerebellum is invaginated beneath the occipital lobes but without compromising cerebrospinal fluid channels enough to cause SM. Thus, broadly defined, CM might be described as any distortion of the skull and craniocervical junction which compromises the neural parenchyma and cerebrospinal fluid circulation causing pain and/or SM. The etiology of CM is multifactorial, potentially including genetically-influenced, breed-specific abnormalities in both skeletal and neural components. Since causation between specific morphologic changes and SM or clinical signs is unproven, CM might be more appropriately considered as a brachycephalic obstructive CSF channel syndrome (BOCCS) rather than a single malformation. Understanding the normal development of the brain, skull and craniocervical junction is fundamental to identifying deviations which predispose to CM/SM. Here we review its anatomical, embryological, bio-mechanical, and genetic underpinnings to update the profession's understanding of this condition and meaningfully inform future research to diminish its welfare impact.
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http://dx.doi.org/10.3389/fvets.2018.00171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6074093PMC
July 2018

Scaling of the corpus callosum in wild and domestic canids: Insights into the domesticated brain.

J Comp Neurol 2018 10 25;526(15):2341-2359. Epub 2018 Sep 25.

School of Anatomical Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, Republic of South Africa.

All domesticated mammals exhibit marked reductions in overall brain size, however, it is unknown whether the corpus callosum (CC), an integral white matter fiber pathway for interhemispheric cortical communication, is affected by domestication differentially or strictly in coordination with changes in brain size. To answer this question, we used quantitative magnetic resonance imaging to compare the midsagittal cross-sectional areas of the CC in 35 carnivore species, including eight wild canids and 13 domestic dogs. We segmented rostro-caudal regions of interest for the CC and evaluated correlations with brain mass. The results of this study indicate that under the influence of domestication in canids, the CC scales to brain size in an allometric relationship that is similar to that of wild canids and other carnivores, with relatively high correlation coefficients observed for all regions, except the rostrum. These results indicate that architectural and energetic considerations are likely to tightly constrain variation in caudal components of the CC relative to overall brain size, however fibers passing through the rostrum, putatively connecting prefrontal cortex, are less constrained and therefore may contribute more toward species-specific differences in connectivity. Given the species diversity of the Canidae and the resurgence of interest in the brain of the domestic dog, further studies aimed at characterizing the neural architecture in domesticated species is likely to provide new insights into the effects of domestication, or artificial selection, on the brain.
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http://dx.doi.org/10.1002/cne.24486DOI Listing
October 2018

Applications and efficiencies of the first cat 63K DNA array.

Sci Rep 2018 05 4;8(1):7024. Epub 2018 May 4.

McDonnell Genome Institute, Washington University School of Medicine, St Louis, MO, USA.

The development of high throughput SNP genotyping technologies has improved the genetic dissection of simple and complex traits in many species including cats. The properties of feline 62,897 SNPs Illumina Infinium iSelect DNA array are described using a dataset of over 2,000 feline samples, the most extensive to date, representing 41 cat breeds, a random bred population, and four wild felid species. Accuracy and efficiency of the array's genotypes and its utility in performing population-based analyses were evaluated. Average marker distance across the array was 37,741 Kb, and across the dataset, only 1% (625) of the markers exhibited poor genotyping and only 0.35% (221) showed Mendelian errors. Marker polymorphism varied across cat breeds and the average minor allele frequency (MAF) of all markers across domestic cats was 0.21. Population structure analysis confirmed a Western to Eastern structural continuum of cat breeds. Genome-wide linkage disequilibrium ranged from 50-1,500 Kb for domestic cats and 750 Kb for European wildcats (Felis silvestris silvestris). Array use in trait association mapping was investigated under different modes of inheritance, selection and population sizes. The efficient array design and cat genotype dataset continues to advance the understanding of cat breeds and will support monogenic health studies across feline breeds and populations.
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http://dx.doi.org/10.1038/s41598-018-25438-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5935720PMC
May 2018

Nationwide genetic testing towards eliminating Lafora disease from Miniature Wirehaired Dachshunds in the United Kingdom.

Canine Genet Epidemiol 2018 27;5. Epub 2018 Mar 27.

1Program in Genetics and Genome Biology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8 Canada.

Background: Canine DNA-testing has become an important tool in purebred dog breeding and many breeders use genetic testing results when planning their breeding strategies. In addition, information obtained from testing of hundreds dogs in one breed gives valuable information about the breed-wide genotype frequency of disease associated allele. Lafora disease is a late onset, recessively inherited genetic disease which is diagnosed in Miniature Wirehaired Dachshunds (MWHD). It is one of the most severe forms of canine epilepsy leading to neurodegeneration and, frequently euthanasia within a few years of diagnosis. Canine Lafora disease is caused by a dodecamer repeat expansion mutation in the gene and a DNA test is available to identify homozygous dogs at risk, carriers and dogs free of the mutation.

Results: Blood samples were collected from 733 MWHDs worldwide, mostly of UK origin, for canine Lafora disease testing. Among the tested MWHD population 7.0% were homozygous for the mutation and at risk for Lafora disease. In addition, 234 dogs were heterozygous, indicating a carrier frequency of 31.9% in the tested population. Among the tested MWHDs, the mutant allele frequency was 0.2. In addition, data from the tested dogs over 6 years (2012-2017) indicated that the frequency of the homozygous and carrier dogs has decreased from 10.4% to 2.7% and 41.5% to 25.7%, respectively among MWHDs tested. As a consequence, the frequency of dogs free of the mutation has increased from 48.1% to 71.6%.

Conclusions: This study provides valuable data for the MWHD community and shows that the DNA test is a useful tool for the breeders to prevent occurrence of Lafora disease in MWHDs. DNA testing has, over 6 years, helped to decrease the frequency of carriers and dogs at risk. Additionally, the DNA test can continue to be used to slowly eradicate the disease-causing mutation in the breed. However, this should be done carefully, over time, to avoid further compromising the genetic diversity of the breed. The DNA test also provides a diagnostic tool for veterinarians if they are presented with a dog that shows clinical signs associated with canine Lafora disease.
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http://dx.doi.org/10.1186/s40575-018-0058-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5869781PMC
March 2018

Feline hyperaesthesia syndrome with self-trauma to the tail: retrospective study of seven cases and proposal for an integrated multidisciplinary diagnostic approach.

J Feline Med Surg 2019 02 29;21(2):178-185. Epub 2018 Mar 29.

1 Hospital for Small Animals, Royal (Dick) School of Veterinary Studies and the Roslin Institute, University of Edinburgh, Edinburgh, UK.

Case Series Summary: This was a retrospective study on the clinical features and response to treatment in seven cats with feline hyperaesthesia syndrome (FHS) and tail mutilation. FHS is a poorly understood disorder characterised by skin rippling over the dorsal lumbar area, episodes of jumping and running, excessive vocalisation, and tail chasing and self-trauma. The majority of the cats were young, with a median age of 1 year at the onset of clinical signs, male (n = 6) and with access to the outdoors (n = 5). Multiple daily episodes of tail chasing and self-trauma were reported in five cats, with tail mutilation in four cats. Vocalisation during the episodes (n = 5) and rippling of lumbar skin (n = 5) were also reported. Haematology, serum biochemistry, Toxoplasma gondii and feline immunodeficiency virus/feline leukaemia virus serology, MRI scans of brain, spinal cord and cauda equina, cerebrospinal fluid analysis and electrodiagnostic tests did not reveal any clinically significant abnormalities. A definitive final diagnosis was not reached in any of the cats, but hypersensitivity dermatitis was suspected in two cases. A variety of medications was used alone or in combination, including gabapentin (n = 6), meloxicam (n = 4), antibiotics (n = 4), phenobarbital (n = 2), prednisolone (n = 2) and topiramate (n = 2); ciclosporin, clomipramine, fluoxetine, amitriptyline and tramadol were used in one cat each. Clinical improvement was achieved in six cases; in five cats complete remission of clinical signs was achieved with gabapentin alone (n = 2), a combination of gabapentin/ciclosporin/amitriptyline (n = 1), gabapentin/prednisolone/phenobarbital (n = 1) or gabapentin/topiramate/meloxicam (n = 1).

Relevance And Novel Information: This is the first retrospective study on a series of cats with FHS. The diagnostic work-up did not reveal any significant abnormalities of the central or peripheral nervous system; dermatological and behavioural problems could not be ruled out. We propose an integrated multidisciplinary diagnostic pathway to be used for the management of clinical cases and for future prospective studies.
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http://dx.doi.org/10.1177/1098612X18764246DOI Listing
February 2019

A genome-wide association study identifies candidate loci associated to syringomyelia secondary to Chiari-like malformation in Cavalier King Charles Spaniels.

BMC Genet 2018 03 22;19(1):16. Epub 2018 Mar 22.

Department of Neurosciences, CHU Sainte Justine Research Center, University of Montréal, 3175 Cote-Sainte-Catherine, Room 3.17.006, Montreal, QC, H3T 1C5, Canada.

Background: Syringomyelia (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.

Results: We 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.

Conclusions: We 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.
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http://dx.doi.org/10.1186/s12863-018-0605-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865342PMC
March 2018

Clinical Application of 3D-CISS MRI Sequences for Diagnosis and Surgical Planning of Spinal Arachnoid Diverticula and Adhesions in Dogs.

Vet Comp Orthop Traumatol 2018 Feb 13;31(2):83-94. Epub 2018 Mar 13.

Neurology Service, Fitzpatrick Referrals, Eashing, United Kingdom.

Objective:  Abnormalities within the spinal arachnoid space are often treated surgically, but they can be challenging to detect with conventional magnetic resonance imaging (MRI) sequences. 3D-CISS sequences are considered superior in evaluating structures surrounded by cerebrospinal fluid (CSF) due to the high signal-to-noise ratio, high contrast-to-noise ratio and intrinsic insensitivity to motion with minimal signal loss due to CSF pulsations. Our objective was to describe findings and advantages in adding 3D-CISS sequences to routine MRI in patients affected by spinal arachnoid diverticula (SAD) or arachnoid adhesions.

Material And Methods:  This article is a retrospective review of medical records of 19 dogs admitted at Fitzpatrick Referrals between 2013 and 2017 that were diagnosed with SAD and confirmed surgically. Inclusion criterions were the presence of clinical signs compatible with compressive myelopathy and an MRI diagnosis, which included the 3D-CISS sequence. Our database was searched for additional 19 dogs diagnosed with other spinal lesions other than SAD that had the same MR sequences. All MR images were anonymized and evaluated by two assessors.

Conclusion And Clinical Relevance:  3D-CISS sequence appears to improve confidence in diagnosing and surgical planning (Mann-Whitney -test:  < 0.0005), delineating SAD from other changes associated with abnormal CSF hydrodynamics and providing more anatomical details than conventional MRI sequences. The clinical data in combination with imaging findings would limit over interpretation, when concurrent pathology within the arachnoid space is present.
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http://dx.doi.org/10.3415/VCOT-16-12-0169DOI Listing
February 2018

Computer simulation of syringomyelia in dogs.

BMC Vet Res 2018 Mar 9;14(1):82. Epub 2018 Mar 9.

The School of Veterinary Medicine, University of Surrey, Guildford, GU2 7AD, UK.

Background: Syringomyelia is a pathological condition in which fluid-filled cavities (syringes) form and expand in the spinal cord. Syringomyelia is often linked with obstruction of the craniocervical junction and a Chiari malformation, which is similar in both humans and animals. Some brachycephalic toy breed dogs such as Cavalier King Charles Spaniels (CKCS) are particularly predisposed. The exact mechanism of the formation of syringomyelia is undetermined and consequently with the lack of clinical explanation, engineers and mathematicians have resorted to computer models to identify possible physical mechanisms that can lead to syringes. We developed a computer model of the spinal cavity of a CKCS suffering from a large syrinx. The model was excited at the cranial end to simulate the movement of the cerebrospinal fluid (CSF) and the spinal cord due to the shift of blood volume in the cranium related to the cardiac cycle. To simulate the normal condition, the movement was prescribed to the CSF. To simulate the pathological condition, the movement of CSF was blocked.

Results: For normal conditions the pressure in the SAS was approximately 400 Pa and the same applied to all stress components in the spinal cord. The stress was uniformly distributed along the length of the spinal cord. When the blockage between the cranial and spinal CSF spaces forced the cord to move with the cardiac cycle, shear and axial normal stresses in the cord increased significantly. The sites where the elevated stress was most pronounced coincided with the axial locations where the syringes typically form, but they were at the perimeter rather than in the central portion of the cord. This elevated stress originated from the bending of the cord at the locations where its curvature was high.

Conclusions: The results suggest that it is possible that repetitive stressing of the spinal cord caused by its exaggerated movement could be a cause for the formation of initial syringes. Further consideration of factors such as cord tethering and the difference in mechanical properties of white and grey matter is needed to fully explore this possibility.
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http://dx.doi.org/10.1186/s12917-018-1410-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845370PMC
March 2018

An Aged Canid with Behavioral Deficits Exhibits Blood and Cerebrospinal Fluid Amyloid Beta Oligomers.

Front Aging Neurosci 2018 30;10. Epub 2018 Jan 30.

Department of Pathology and Infectious Diseases, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom.

Many of the molecular and pathological features associated with human Alzheimer disease (AD) are mirrored in the naturally occurring age-associated neuropathology in the canine species. In aged dogs with declining learned behavior and memory the severity of cognitive dysfunction parallels the progressive build up and location of Aβ in the brain. The main aim of this work was to study the biological behavior of soluble oligomers isolated from an aged dog with cognitive dysfunction through investigating their interaction with a human cell line and synthetic Aβ peptides. We report that soluble oligomers were specifically detected in the dog's blood and cerebrospinal fluid (CSF) via anti-oligomer- and anti-Aβ specific binders. Importantly, our results reveal the potent neurotoxic effects of the dog's CSF on cell viability and the seeding efficiency of the CSF-borne soluble oligomers on the thermodynamic activity and the aggregation kinetics of synthetic human Aβ. The value of further characterizing the naturally occurring Alzheimer-like neuropathology in dogs using genetic and molecular tools is discussed.
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http://dx.doi.org/10.3389/fnagi.2018.00007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797595PMC
January 2018

MRI characteristics for "phantom" scratching in canine syringomyelia.

BMC Vet Res 2017 Nov 16;13(1):340. Epub 2017 Nov 16.

School of Veterinary Medicine, Faculty of Health & Medical Sciences, Daphne Jackson Road, Guildford, Surrey, GU2 7AL, UK.

Background: A classic sign of canine syringomyelia (SM) is scratching towards one shoulder. Using magnetic resonance imaging (MRI) we investigate the spinal cord lesion relating to this phenomenon which has characteristics similar to fictive scratch secondary to spinal cord transection. Medical records were searched for Cavalier King Charles spaniels with a clinical and MRI diagnosis of symptomatic SM associated with Chiari-like malformation (CM). The cohort was divided into SM with phantom scratching (19 dogs) and SM but no phantom scratching (18 dogs). MRI files were anonymised, randomised and viewed in EFILM ™. For each transverse image, the maximum perpendicular dimensions of the syrinx in the dorsal spinal cord quadrants were determined. Visual assessment was made as to whether the syrinx extended to the superficial dorsal horn (SDH).

Results: We showed that phantom scratching appears associated with a large dorsolateral syrinx that extends to the SDH in the C3-C6 spinal cord segments (corresponding to C2-C5 vertebrae). Estimated dorsal quadrant syrinx sizes based on the perpendicular diameters were between 2.5 and 9.5 times larger in dogs with phantom scratching, with the largest mean difference p-value being 0.009.

Conclusion: SM associated phantom scratching appears associated with MRI findings of a large syrinx extending into the mid cervical SDH. We hypothesise that damage in this region might influence the lumbosacral scratching central pattern generator (CPG). If a scratching SM affected dog does not have a large dorsolateral cervical syrinx with SDH involvement then alternative explanations for scratching should be investigated.
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http://dx.doi.org/10.1186/s12917-017-1258-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5691609PMC
November 2017
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