Professor Clare Rusbridge


Professor in Veterinary Neurology
BVMS PhD DECVN FRCVS
+44 (0)1483 682322
01 VSM 02
Thursday and Friday

Academic and research departments

School of Veterinary Medicine.

Biography

Biography

Dr Clare Rusbridge graduated from the University of Glasgow in 1991 and following an internship at the University of Pennsylvania and general practice in Cambridgeshire, she completed a BSAVA/Petsavers Residency and was Staff Clinician in Neurology at the Royal Veterinary College. She became a Diplomate of the European College of Veterinary Neurology in 1996 and a RCVS Specialist in 1999. In 2007 she was awarded a PhD from Utrecht University for her thesis on Chiari-like malformation & Syringomyelia.  For 16 years she operated a neurology and neurosurgery referral service at the Stone Lion Veterinary Hospital in Wimbledon. In September 2013 Clare joined Fitzpatrick Referrals and the University of Surrey. Her professional interests include epilepsy, neuropathic pain, inherited diseases, and rehabilitation following spinal injury. She treats many animals with painful and/or distressing inherited disease which motivates her research aiming to find a better way of diagnosing, treating and preventing these conditions. She was awarded the J. A. Wright (a.k.a. James Herriot) Memorial Award by The Blue Cross Animal Welfare Charity in 2011 for her work with syringomyelia, in 2014 she received the FECVA award for best original paper also on syringomyelia and in 2016 she was made a Fellow of the Royal College of Veterinary Surgeons for meritorious contribution to knowledge. Clare is has authored or co-authored over 90 scientific articles and book chapters including being co-editor for a medical textbook on Syringomyelia published by Springer.

Research Interests

MRI conformational changes and dysmorphia associated with Chiari malformation

Clare provided the first description of this disease in the dog published in 2000 and came to realize quickly that this disorder was more than “cerebellar herniation” and was actually an extremely complex malformation of the skull and cervical vertebrae linked to brachycephalic head and facial characteristics. Understanding the way these conformation changes impact nervous tissue compliance and cerebrospinal fluid channels is key to understanding the pathogenesis of syringomyelia.  Clare been primary, co-investigator or supervisor in over 20 projects on the morphometric changes associated with Chiari malformation and its association to syringomyelia. She has a close collaboration with Dr Kevin Wells (Reader in Medical Imaging) and Dr Serge Cirovic (Lecturer in Biomedical Engineering) both of whom are pivotal in helping to find engineering solutions to the clinical problems that she is trying to solve. 

Genetics of Chiari malformation and syringomyelia

Since 2005, Clare Rusbridge and collaborator Dr Penny Knowler have had a partnership with Dr Kibar’s group of the University of Montreal with an aim of identifying genetic markers for canine CMSM and to translate the findings into genomic studies on humans. Prior to joining Surrey University they established a large database of DNA linked to MRI findings and over the last decade have refined phenotypical analysis of affected dogs and their diagnostic MRI in parallel with advances in statistical genetic analysis. Recently they identified strong candidate genes for CM in dogs and humans and SM in dogs which can be directly correlated to MRI morphometric traits and clinical findings of neuropathic pain. These findings have impact on understanding of the osseous changes in CM and why some patients are painful. In collaboration with the Medical Imaging Group at the University of Surrey they are now applying a machine learning approach to the significant MRI morphometric traits to establish a simple objective measure that could be applied to future genetic and other studies and develop a medical image analysis software that can be used to screen susceptible breeding dogs and be translated into human studies.

Progressive myoclonic epilepsy (Lafora’s disease)

Clare is the chief veterinary collaborator for an ongoing project on Lafora disease (a polyglucasan storage disease). After identifying this rare progressive myoclonic epilepsy in a canine patient in 2001, Clare established links with Dr. Berge Minassian of the Hospital for Sick Children, University of Toronto to study the mutation causing the disease. They established a nationwide program of DNA collection from affected dogs and their relatives to conduct a genome scan and characterization of the mutation. The successful outcome was the first description of a mutation causing canine epilepsy and the first example of a tandem repeat expansion outside of humans. This has led to better understanding of the disease in humans. In addition, a test for detection of affected and carrier dogs was established to enable a controlled breeding program in affected dog breeds. In the near future Clare hopes to establish a preventative treatment program that could be translated for human patients

Canine and feline epilepsy

Clare has been a member of the International Veterinary Epilepsy Task Force since its conception in 2013. This team’s mission statement is to suggest consensus statements and provide definitions for canine and feline epilepsy and to advance the field by doing collaborative research and exchanging ideas. Clare led the diagnostic imaging subgroup. So far the IVETF have produced seven consensus statements on the diagnosis, classification, treatment and genetics of canine epilepsy and one investigative study.

Affiliations

Other Professional and Academic Activities

  • The Dog Breeding Reform Group. The DBRG promote humane behaviour towards animals by providing and supporting initiatives to improve dog welfare related to: a) genetic and breed related health, breeding, rearing and selling practices; and b) to inform the general public about irresponsible dog breeding in order to make them aware of the potential impact on their dogs' health and welfare. DBRG was the CEVA Charity team of the Year 2018
  • The Advisory Council for Welfare Breeding Pedigree Dogs - The role of the Council was to encourage and facilitate significant improvements in the welfare issues associated with dog breeding by providing independent, expert advice to governments and other stakeholders. Clare was appointed to this panel in 2010, from its inception until it retired in 2014.
  • Scrutineer British Veterinary Association/Kennel Club CMSM MRI screening scheme - Clare played a pivotal role in establishing this scheme and has been a scruitneer since its inception.
  • International Veterinary Epilepsy Task Force- Clare is part of a multicentre task force, firstly to suggest consensus statements and provide definitions for canine and feline epilepsy, and secondly to advance the field by doing collaborative research and exchanging ideas.
  • Clare is a member of the British Syringomyelia Group - a group of neurosurgeons involved in the treatment of syringomyelia and has been awarded Honorary Friendship of the Ann Conroy Trust 
  • Phyllis Croft Foundation for Canine Epilepsy - Clare is the veterinary advisory for this charity.

Scientific Journals

  • Clare is a regular reviewer of scientific articles for BMC Veterinary,  Veterinary Comparative Orthopedics and Traumatology, Journal of Small Animal Practice, Veterinary Record, Veterinary Radiology and Ultrasound, American Journal of Veterinary Research, Journal of Veterinary Internal Medicine and occasionally other journals including Plos One and Nature.

Supervision

Postgraduate research supervision

Postgraduate research supervision

Courses I teach on

Undergraduate

My publications

Publications

Driver C, Volk H, Rusbridge C, Van Ham L (2013) An update on the pathogenesis of syringomyelia secondary to Chiari-like malformations in dogs., Vet J 198 (3) pp. 551-559
Syringomyelia (SM) is a spinal cord disease that can cause neuropathic pain in dogs. The pathogenesis of SM secondary to Chiari-like malformation (CM) has been the focus of intense research in recent years. The gulf in our understanding of CM/SM in dogs relative to the analogous human condition has progressively narrowed. CM is primarily a disease of abnormal geometric morphometry affecting the caudal cranial fossa and the brain parenchyma contained within it. This review describes how advanced imaging techniques have revealed a series of morphometric abnormalities associated with CM/SM. The series is presented in a logical order to help describe the pathogenesis of CM and the subsequent formation of syringes, with particular reference to the concepts of craniospinal compliance and cerebrospinal fluid pulse pressure timing.
Jokinen TS, Rusbridge C, Steffen F, Viitmaa R, Syrjä P, De Lahunta A, Snellman M, Cizinauskas S (2007) Cerebellar cortical abiotrophy in Lagotto Romagnolo dogs., J Small Anim Pract 48 (8) pp. 470-473
This case report documents two pathological variations of potentially inherited, cerebellar cortical abiotrophy in two unrelated Lagotto Romagnolo breed dogs. The first dog had an atypical lesion in the cerebellar cortex with depletion of cerebellar granular cell layer and sparing of the Purkinje cell layer. The second case had degenerative changes in both Purkinje and granular cell layers. The clinical picture was similar in both cases presented, although the severity of the signs of cerebellar dysfunction varied.
Plessas I, Volk H, Rusbridge C, Vanhaesebrouck A, Jeffery N (2015) Comparison of gabapentin versus topiramate on clinically affected dogs with Chiari-like malformation and syringomyelia, VETERINARY RECORD 177 (11) pp. 288-+ BMJ PUBLISHING GROUP
Tauro A, Addicott D, Foale RD, Bowman C, Hahn C, Long S, Massey J, Haley AC, Knowler SP, Day MJ, Kennedy LJ, Rusbridge C (2015) Clinical features of idiopathic inflammatory polymyopathy in the Hungarian Vizsla., BMC Vet Res 11
BACKGROUND: A retrospective study of the clinicopathological features of presumed and confirmed cases of idiopathic inflammatory polymyopathy in the Hungarian Vizsla dog and guidelines for breeding. RESULTS: 369 medical records were reviewed (1992-2013) and 77 Hungarian Vizslas were identified with a case history consistent with idiopathic inflammatory polymyopathy. Inclusion criteria were: group 1 (confirmed diagnosis); histopathology and clinical findings compatible with an inflammatory polymyopathy and group 2 (probable diagnosis); clinical findings compatible with a polymyopathy including dysphagia, sialorrhea, temporal muscle atrophy, elevated serum creatine kinase (CK) activity, and sufficient clinical history to suggest that other neuromuscular disorders could be ruled out. Some group 2 dogs had muscle biopsy, which suggested muscle disease but did not reveal an inflammatory process. The mean age of onset was 2.4 years; male dogs were slightly overrepresented. Common presenting signs were dysphagia, sialorrhea, masticatory muscle atrophy, and regurgitation. Common muscle histopathological findings included degenerative and regenerative changes, with multifocal mononuclear cell infiltration with lymphoplasmacytic myositis of variable severity. A positive response to immunosuppressive treatment supported an immune-mediated aetiology. The mean age at death and survival time were 6.4 and 3.9 years, respectively. Recurrence of clinical signs and aspiration pneumonia were common reasons for euthanasia. CONCLUSIONS: Diagnosis of Vizsla idiopathic inflammatory polymyopathy can be challenging due to lack of specific tests, however the presence of dysphagia, regurgitation and masticatory muscle atrophy in this breed with negative serological tests for masticatory muscle myositis and myasthenia gravis, along with muscle biopsies suggesting an inflammatory process, support the diagnosis. However, there is an urgent need for a more specific diagnostic test. The average of inbreeding coefficient (CoI) of 16.3% suggests an increased expression of a Dog Leukocyte Antigen Class II haplotype, leading to an increased disease risk. The prognosis remains guarded, as treatment can only manage the disease. Recurrence of clinical signs and perceived poor quality of life are the most common reasons for humane euthanasia.
Rusbridge C, Knowler SP (2006) Coexistence of occipital dysplasia and occipital hypoplasia/syringomyelia in the cavalier King Charles spaniel., J Small Anim Pract 47 (10) pp. 603-606
Concurrent occurrence of occipital dysplasia and occipital hypoplasia in two dogs is described in this report. Occipital hypoplasia results in reduced volume of the caudal fossa, leading to overcrowding of the neural structures and, in severe cases, development of syringomyelia. In occipital dysplasia, there is a failure of complete ossification of the supraoccipital bone. When the two conditions occur concurrently, it is possible that syringomyelia may develop more slowly, resulting in presentation with clinical signs in middle to old age. This has implications for screening tests for early detection of syringomyelia, with a view to using the dog for breeding purposes, as dogs with an apparently mild phenotype for occipital hypoplasia/syringomyelia may actually have a more severe genotype.
Mandigers P, Rusbridge C (2009) [Chiari-like malformation--syringomyelia in the Cavalier King Charles Spaniel]., Tijdschr Diergeneeskd 134 (18) pp. 746-750
This article, which is based on the PhD thesis of Clare Rusbridge, is a review of chiari-like malformation and syringomyelia in the Cavalier King Charles Spaniel. The abnormality is becoming more common among dwarf breeds and brachychepalic breeds. The nature, prevalence, and treatment of the disease are described, as is current knowledge on its heritability in the Cavalier King Charles Spaniel.
Knowler SP, McFadyen AK, Rusbridge C (2011) Effectiveness of breeding guidelines for reducing the prevalence of syringomyelia, Veterinary Record 169 (26)
Several toy breed dogs are predisposed to syringomyelia (SM), a spinal cord disorder, characterised by fluid-filled cavitation. SM is a complex trait with a moderately high heritability. Selective breeding against SM is confounded by its complex inheritance, its late onset nature and high prevalence in some breeds. This study investigated the early outcome of existing SM breeding guidelines. Six hundred and forty-three dogs, 550 Cavalier King Charles spaniels (CKCS) and 93 Griffon Bruxellois (GB), were identified as having either one (454 dogs) or both parents (189 dogs) with MRI-determined SM status. Offspring without SM were more common when the parents were both clear of SM (SM-free; CKCS 70 per cent, GB 73 per cent). Conversely, offspring with SM were more likely when both parents had SM (SM-affected; CKCS 92 per cent, GB 100 per cent). A mating of one SM-free parent with an SM-affected parent was risky for SM affectedness with 77 per cent of CKCS and 46 per cent of GB offspring being SM-affected. It is recommended that all breeding dogs from breeds susceptible to SM be MRI screened; that the SM status at five years old is established; and all results submitted to a central database that can be used by dog breeders to better enable mate selection based on estimated breeding values.
Driver CJ, De Risio L, Hamilton S, Rusbridge C, Dennis R, McGonnell IM, Volk HA (2012) Changes over time in craniocerebral morphology and syringomyelia in cavalier King Charles spaniels with Chiari-like malformation., BMC Vet Res 8
Chiari-like malformation (CM) and syringomyelia is a neurological disease complex with high prevalence in cavalier King Charles spaniels (CKCS). The natural progression of this disease with time has not been described. The objectives of this study were to i) determine if syringomyelia progresses with time ii) determine if features of craniocrebral morphology previously associated with CM are progressive (including caudal cranial fossa volume, caudal cranial fossa parenchymal volume, ventricular dimensions, height of the foramen magnum and degree of cerebellar herniation). A retrospective morphometric analysis was undertaken in 12 CKCS with CM for which repeat magnetic resonance images were available without surgical intervention.
Rusbridge C, Heath S, Gunn-Moore DA, Knowler SP, Johnston N, McFadyen AK (2010) Feline orofacial pain syndrome (FOPS): A retrospective study of 113 cases, Journal of Feline Medicine and Surgery 12 (6) pp. 498-508
Feline orofacial pain syndrome (FOPS) is a pain disorder of cats with behavioural signs of oral discomfort and tongue mutilation. This report describes the findings from a case series of 113 cats including 100 Burmese. FOPS is suspected to be a neuropathic pain disorder and the predominance within the Burmese cat breed suggests an inherited disorder, possibly involving central and/or ganglion processing of sensory trigeminal information. The disease is characterised by an episodic, typically unilateral, discomfort with pain-free intervals. The discomfort is triggered, in many cases, by mouth movements. The disease is often recurrent and with time may become unremitting - 12% of cases in this series were euthanased as a consequence of the condition. Sensitisation of trigeminal nerve endings as a consequence of oral disease or tooth eruption appears to be an important factor in the aetiology - 63% of cases had a history of oral lesions and at least 16% experienced their first sign of discomfort during eruption of permanent teeth. External factors can also influence the disease as FOPS events could be directly linked to a situation causing anxiety in 20% of cats. FOPS can be resistant to traditional analgesics and in some cases successful management required anti-convulsants with an analgesic effect. © 2010 ISFM and AAFP.
Rusbridge C (2013) Choosing the right drug 2. Anticonvulsants used for second-line therapy, other anticonvulsants and alternative therapies, In Practice 35 (4) pp. 183-189
Many epileptic patients will have satisfactory seizure control using the first-line anticonvulsants phenobarbital and/or bromide, as discussed in the first article of this series (In Practice, March 2013, vol 35, pp 106-113). However, some patients will continue to have an unacceptable number or severity of seizures despite adequate drug serum concentrations. Some patients have a compromised quality of life because of the adverse effects of their medication. In this article, the anticonvulsant drugs used for second-line therapy are discussed, together with other anticonvulsants and alternative therapies.
Packer RM, Berendt M, Bhatti S, Charalambous M, Cizinauskas S, De Risio L, Farquhar R, Hampel R, Hill M, Mandigers PJ, Pakozdy A, Preston SM, Rusbridge C, Stein VM, Taylor-Brown F, Tipold A, Volk HA (2015) Inter-observer agreement of canine and feline paroxysmal event semiology and classification by veterinary neurology specialists and non-specialists., BMC Vet Res 11
BACKGROUND: Advances in mobile technology mean vets are now commonly presented with videos of paroxysmal events by clients, but the consistency of the interpretation of these videos has not been investigated. The objective of this study was to investigate the level of agreement between vets (both neurology specialists and non-specialists) on the description and classification of videos depicting paroxysmal events, without knowing any results of diagnostic workup. An online questionnaire study was conducted, where participants watched 100 videos of dogs and cats exhibiting paroxysmal events and answered questions regarding: epileptic seizure presence (yes/no), seizure type, consciousness status, and the presence of motor, autonomic and neurobehavioural signs. Agreement statistics (percentage agreement and kappa) calculated for each variable, with prevalence indices calculated to aid their interpretation. RESULTS: Only a fair level of agreement (º = 0.40) was found for epileptic seizure presence. Overall agreement of seizure type was moderate (º = 0.44), with primary generalised seizures showing the highest level of agreement (º = 0.60), and focal the lowest (º =0.31). Fair agreement was found for consciousness status and the presence of autonomic signs (º = 0.21-0.40), but poor agreement for neurobehavioral signs (º = 0.16). Agreement for motor signs ranged from poor (º = d 0.20) to moderate (º = 0.41-0.60). Differences between specialists and non-specialists were identified. CONCLUSIONS: The relatively low levels of agreement described here highlight the need for further discussions between neurology experts regarding classifying and describing epileptic seizures, and additional training of non-specialists to facilitate accurate diagnosis. There is a need for diagnostic tools (e.g. electroencephalogram) able to differentiate between epileptic and non-epileptic paroxysms.
Freeman A, Platt S, Kent M, Huguet E, Rusbridge C, Holmes S (2014) Chiari-Like Malformation and Syringomyelia in American Brussels Griffon Dogs, JOURNAL OF VETERINARY INTERNAL MEDICINE 28 (5) pp. 1551-1559 WILEY-BLACKWELL
BACKGROUND: Although Chiari-like malformation (CM) and syringomyelia (SM) have been described in many small breed dogs, the prevalence and clinical manifestations of this complex have not been documented in a large cohort of American Brussels Griffon (ABG) dogs. OBJECTIVES: To characterize the clinical and magnetic resonance imaging (MRI) features of CM and SM in the ABG breed. ANIMALS: Eighty-four American Kennel Club registered ABG dogs were recruited. METHODS: Prospective study. Complete histories and neurologic examinations were obtained before MRI. Images were blindly reviewed and calculations were made by using OsiriX. All analyses were performed by Student's t-test, Spearman's correlation, ANOVA, and chi-square test where appropriate. RESULTS: Chiari-like malformation and SM were present in 65% and 52% of dogs, respectively. Twenty-eight percent of dogs had neurologic deficits and 20% had neck pain. Mean central canal (CC) transverse height was 2.5 mm with a mean length of 3.6 cervical vertebrae. Neurologic deficits were significantly associated with a larger syrinx (P = .04, P = .08) and syrinx size increased with age (P = .027). SM was associated with a smaller craniocervical junction (CCJ) height (P = .04) and larger ventricles (P = .0001; P
Matiasek K, Pumarola i Batlle M, Rosati M, Fernandez-Flores F, Fischer A, Wagner E, Berendt M, Bhatti S, De Risio L, Farquhar R, Long S, Munana K, Patterson E, Pakozdy A, Penderis J, Platt S, Podell M, Potschka H, Rusbridge C, Stein V, Tipold A, Volk H (2015) International veterinary epilepsy task force recommendations for systematic sampling and processing of brains from epileptic dogs and cats, BMC VETERINARY RESEARCH 11 ARTN 216 BIOMED CENTRAL LTD
Rusbridge C (2007) Chiari-like malformation with syringomyelia in the Cavalier King Charles spaniel: long-term outcome after surgical management., Vet Surg 36 (5) pp. 396-405
OBJECTIVE: To evaluate long-term success of cranial cervical decompression for management of canine Chiari-like malformation with syringomyelia (CM/SM). STUDY DESIGN: Retrospective clinical study. ANIMALS: Cavalier King Charles spaniels (n=15). METHODS: After diagnosis by magnetic resonance imaging (MRI) dogs had cranial cervical decompression with durotomy. Seven dogs had the durotomy patched with biocompatible collagen matrix. Clinical outcome was monitored for >12 months. RESULTS: All dogs either improved (80%) or were unchanged (20%) postoperatively. Postoperative MRI in 6 dogs revealed persistence of syringomyelia. Seven dogs (47%) subsequently deteriorated, 0.2-2.3 years after surgery (mean, 1.3 years) and 2 dogs were eventually euthanatized as a consequence. Twelve dogs were still alive, 1-6.5 years after surgery (mean, 2.5 years). CONCLUSION: Cranial cervical decompression surgery is associated with low mortality and morbidity, and results in clinical improvement in most dogs. The procedure seemingly does not result in syrinx collapse and resolution. Clinical improvement may not be sustained and some dogs can be expected to deteriorate. CLINICAL RELEVANCE: Cranial cervical decompression surgery may have a role in management of CM/SM. In dogs with severe pain, it can improve quality of life for several years; however, it does not appear to adequately address the primary cause of syringomyelia. Further prospective study is needed to better understand the pathogenesis and treatment of this disorder. Because this condition causes neuropathic pain but does not necessarily result in euthanasia more information is needed on appropriate pain management for these patients.
Loderstedt S, Benigni L, Chandler K, Cardwell JM, Rusbridge C, Lamb CR, Volk HA (2011) Distribution of syringomyelia along the entire spinal cord in clinically affected Cavalier King Charles Spaniels, Veterinary Journal 190 (3) pp. 359-363
Chiari-like malformation (CM) and syringomyelia (SM) is an important disease complex in the Cavalier King Charles Spaniel (CKCS) but data about the anatomical distribution of SM along the spinal cord are lacking in veterinary medicine. The objective of this study was to define the anatomic distribution of SM in CKCS clinically affected by CM/SM. Magnetic resonance imaging (MRI) of the brain and the entire spinal cord of 49 dogs was performed and different morphological parameters compared.Syrinx formation was present in the C1-C4 region and in other parts of the spinal cord. The maximal dorsoventral syrinx size can occur in any region of the spinal cord and the total syrinx size was positively correlated with age. Seventy-six per cent of CKCS with a cranial cervical syrinx also have a syrinx affecting more caudal spinal cord regions. MRI restricted to the cervical region may underestimate the extent of SM and the severity of the disease process in the majority of dogs. © 2010 Elsevier Ltd.
Lewis T, Rusbridge C, Knowler P, Blott S, Woolliams JA (2010) Heritability of syringomyelia in Cavalier King Charles spaniels, Veterinary Journal 183 (3) pp. 345-347
Mixed model analysis of 384 Cavalier King Charles spaniels (CKCS), with a magnetic resonance imaging diagnosis for the presence or absence of a syrinx, in conjunction with the Kennel Club pedigree records of all dogs registered from the mid 1980s to September 2007, revealed a moderately high estimate of heritability of syringomyelia (h2 = 0.37 ± 0.15 standard error) when analysed as a binary trait. Inspection of cases where the disease segregated within families pointed to genes at more than one locus influencing syringomyelia. The availability of estimated breeding values for Kennel Club registered CKCS is a significant step in being able to select against syringomyelia, particularly given the difficulty of ascertaining the disease phenotype. © 2009 Elsevier Ltd. All rights reserved.
Stalin CE, Rusbridge C, Granger N, Jeffery ND (2008) Radiographic morphology of the cranial portion of the cervical vertebral column in Cavalier King Charles Spaniels and its relationship to syringomyelia., Am J Vet Res 69 (1) pp. 89-93
OBJECTIVE: To compare radiographic morphology of the atlantoaxial region between Cavalier King Charles Spaniels (CKCSs) and dogs of other breeds and determine whether there was an association between radiographic morphology of the atlantoaxial region and syringomyelia in CKCSs. ANIMALS: 65 CKCSs and 72 dogs of other breeds. PROCEDURES: The amount that the spinous process of the axis overlapped the dorsal arch of the atlas, the relative size of the spinous process of the axis, and the amount of widening of the atlantoaxial joint that occurred when the neck was moved from a neutral to a flexed position were measured on lateral radiographic projections of the atlantoaxial region. Magnetic resonance images were reviewed to identify CKCSs with syringomyelia. RESULTS: The amount of overlap of the atlas and axis and the relative size of the spinous process of the axis were significantly smaller in CKCSs than in dogs of other breeds. However, the amount of widening of the atlantoaxial joint that occurred when the neck was moved from a neutral to a flexed position was not significantly different between groups, and no association was detected between syringomyelia and excessive atlantoaxial joint space widening or between syringomyelia and an excessively small axial spinous process. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that radiographic morphology of the atlantoaxial region in CKCSs differs from morphology of that region in dogs of other breeds, but that these differences do not account for why some CKCSs develop syringomyelia and others do not.
Huelsmeyer V, Fischer A, Mandigers P, DeRisio L, Berendt M, Rusbridge C, Bhatti S, Pakozdy A, Patterson E, Platt S, Packer R, Volk H (2015) International Veterinary Epilepsy Task Force's current understanding of idiopathic epilepsy of genetic or suspected genetic origin in purebred dogs, BMC VETERINARY RESEARCH 11 ARTN 175 BIOMED CENTRAL LTD
Mitchell T, Knowler S, van den Berg H, Sykes J, Rusbridge C (2014) Syringomyelia: determining risk and protective factors in the conformation of the Cavalier King Charles Spaniel dog., Canine Genet Epidemiol 1 BioMed Central
BACKGROUND:

Syringomyelia (SM) is a painful neurological condition, prevalent in brachycephalic toy breeds including the Cavalier King Charles Spaniel (CKCS). In these breeds, SM is typically secondary to Chiari-like Malformation (CM). There has been much debate in the scientific and veterinary communities to what extent head shape is indicative of either pathology, especially as certain craniosynostosis syndromes in humans (highly associated with CM) have characteristic facial and cranial morphologies. Elucidating a risk morphology would allow for selection away from these traits and proffer further breeding guidelines for the condition. Dogs were measured in multiple countries by means of a standardised bony landmark measuring protocol and photo analysis by blinded, trained researchers.

RESULTS:

The results found two significant risk factors in the conformation of the CKCS: extent of brachycephaly and distribution of cranium. The study identified a greater amount of cranium distributed caudally (relative to the amount distributed rostrally) to be significantly protective against syrinx development at the levels of three years of age, five years of age and when comparing a sample of SM clear individuals over the age of five to those affected younger than three years of age. A decreased cephalic index (decreasing brachycephaly) was significantly protective at the latter level. Cephalic index and caudal cranium distribution exhibited a negative, linear relationship. Cephalic index demonstrated a positive linear relationship with the amount of doming of the head.

CONCLUSIONS:

This study proposes a risk phenotype of brachycephaly with resulting rostrocaudal doming that is more rostrally distributed and hence sloping caudally. The results of this study may allow for selection against risk aspects of conformation in the CKCS in combination with the British Veterinary Association/Kennel Club CM/SM scheme to enable reduction in CM/SM incidence. Further research comparing this external risk phenotype to the internal presentation upon MRI would determine how these features are indicative of syrinx development. Utilising breeds in which CM free individuals are more available may allow for validation of this risk phenotype for CM or determine alternatives.

Flint G, Rusbridge C (2014) Syringomyelia: A Disorder of CSF Circulation, Springer-Verlag Berlin Heidelberg
Syringomelia is a relatively rare clinical entity in which fluid-filled cavities develop within the spinal cord. Although modern imaging technologies usually permit an accurate diagnosis at an early stage, syringomyelia remains an enigmatic condition. This reference monograph provides an up-to-date account of the present state of understanding of syringomyelia and related disorders. The editors aim to document the best clinical practice in diagnosis and treatment and to provide clear guidance on how to reduce the incidence of severe outcomes. New challenges are addressed, including the appropriate management of the increasing number of apparently idiopathic syrinx cavities that are detected. In addition, controversies in current practice and directions for future research are fully discussed. Syringomelia will be an invaluable source of information for experts in the field, specialists in various related disciplines and other interested health care professionals.
Freeman AC, Platt SR, Kent M, Huguet E, Rusbridge C, Holmes S (2014) Chiari-Like Malformation and Syringomyelia in American Brussels Griffon Dogs, Journal of Veterinary Internal Medicine 28 (5) pp. 1551-1559
© 2014 by the American College of Veterinary Internal Medicine.Background: Although Chiari-like malformation (CM) and syringomyelia (SM) have been described in many small breed dogs, the prevalence and clinical manifestations of this complex have not been documented in a large cohort of American Brussels Griffon (ABG) dogs. Objectives: To characterize the clinical and magnetic resonance imaging (MRI) features of CM and SM in the ABG breed. Animals: Eighty-four American Kennel Club registered ABG dogs were recruited. Methods: Prospective study. Complete histories and neurologic examinations were obtained before MRI. Images were blindly reviewed and calculations were made by using OsiriX. All analyses were performed by Student's t-test, Spearman's correlation, ANOVA, and chi-square test where appropriate. Results: Chiari-like malformation and SM were present in 65% and 52% of dogs, respectively. Twenty-eight percent of dogs had neurologic deficits and 20% had neck pain. Mean central canal (CC) transverse height was 2.5 mm with a mean length of 3.6 cervical vertebrae. Neurologic deficits were significantly associated with a larger syrinx (P = .04, P = .08) and syrinx size increased with age (P = .027). SM was associated with a smaller craniocervical junction (CCJ) height (P = .04) and larger ventricles (P = .0001; P
Background: Feline idiopathic ulcerative dermatosis is a rare, poorly understood condition characterized by self-trauma. The lesion presents as a nonhealing, crusted ulcer, which occurs most commonly on the dorsal midline of the neck or between the scapulae. Animal: A 2-year-old female neutered domestic short hair cat was presented with an ulcerative dermatosis affecting the dorsal midline. Previous investigations had failed to identify the cause, and the lesion was resistant to treatment. Methods and results: Diagnosis was based on clinical findings and confirmed by histopathology showing epidermal ulceration and superficial necrosis with a mild dermal infiltrate together with subepidermal fibrosis. The cat had been fed a commercial hypoallergenic diet for 6 months, which had successfully managed its chronic diarrhoea. Deep skin scrapings, cytology and fungal culture failed to demonstrate pathogens. Conclusions and clinical importance: Remission was obtained within 4 weeks and has been maintained over a 30 month period with topiramate (5 mg/kg orally twice daily), an anti-epileptic drug used in human medicine. Attempts to withdraw this therapy led to relapse within 24 h on two occasions. To the best of the authors' knowledge, this is the first case report of the use of this drug for feline idiopathic ulcerative dermatosis. © 2014 ESVD and ACVD.
Knowler SP, McFadyen AK, Freeman C, Kent M, Platt SR, Kibar Z, Rusbridge C (2014) Quantitative analysis of Chiari-like malformation and syringomyelia in the griffon bruxellois dog., PLoS One 9 (2)
This study aimed to develop a system of quantitative analysis of canine Chiari-like malformation and syringomyelia on variable quality MRI. We made a series of measurements from magnetic resonance DICOM images from Griffon Bruxellois dogs with and without Chiari-like malformation and syringomyelia and identified several significant variables. We found that in the Griffon Bruxellois dog, Chiari-like malformation is characterized by an apparent shortening of the entire cranial base and possibly by increased proximity of the atlas to the occiput. As a compensatory change, there appears to be an increased height of the rostral cranial cavity with lengthening of the dorsal cranial vault and considerable reorganization of the brain parenchyma including ventral deviation of the olfactory bulbs and rostral invagination of the cerebellum under the occipital lobes.
Massey J, Rothwell S, Rusbridge C, Tauro A, Addicott D, Chinoy H, Cooper RG, Ollier WE, Kennedy LJ (2013) Association of an MHC class II haplotype with increased risk of polymyositis in Hungarian Vizsla dogs., PLoS One 8 (2)
A breed-specific polymyositis is frequently observed in the Hungarian Vizsla. Beneficial clinical response to immunosuppressive therapies has been demonstrated which points to an immune-mediated aetiology. Canine inflammatory myopathies share clinical and histological similarities with the human immune-mediated myopathies. As MHC class II associations have been reported in the human conditions we investigated whether an MHC class II association was present in the canine myopathy seen in this breed. 212 Hungarian Vizsla pedigree dogs were stratified both on disease status and degree of relatedness to an affected dog. This generated a group of 29 cases and 183 "graded" controls: 93 unaffected dogs with a first degree affected relative, 44 unaffected dogs with a second degree affected relative, and 46 unaffected dogs with no known affected relatives. Eleven DLA class II haplotypes were identified, of which, DLA-DRB1*02001/DQA1*00401/DQB1*01303, was at significantly raised frequency in cases compared to controls (OR
=
1.92, p
=
0.032). When only control dogs with no family history of the disease were compared to cases, the association was further strengthened (OR
=
4.08, p
=
0.00011). Additionally, a single copy of the risk haplotype was sufficient to increase disease risk, with the risk substantially increasing for homozygotes. There was a trend of increasing frequency of this haplotype with degree of relatedness, indicating low disease penetrance. These findings support the hypothesis of an immune-mediated aetiology for this canine myopathy and give credibility to potentially using the Hungarian Vizsla as a genetic model for comparative studies with human myositis.
Rusbridge C (2015) Syringomyelia and Chiari malformation, In: Tilley L, Smith F (eds.), Blackwell's Five-Minute Veterinary Consult: Canine and Feline pp. 1289-1290 Wiley-Blackwell
Rusbridge C (2016) Tremors, In: Ettinger SJ, Feldman EC, Cote E (eds.), Textbook of Veterinary Internal Medicine 32 pp. 130-133 Saunders
Driver CJ, Rusbridge C, Cross HR, McGonnell I, Volk HA (2010) Relationship of brain parenchyma within the caudal cranial fossa and ventricle size to syringomyelia in cavalier King Charles spaniels, Journal of Small Animal Practice 51 (7) pp. 382-386
Objectives: To assess if the volumes of the caudal cranial fossa (CCF), parenchyma within the caudal cranial fossa (CCFP) or ventricles (V) are associated with syringomyelia (SM) in cavalier King Charles spaniels (CKCS) with Chiari-like malformation (CM). To evaluate if volumes are associated with transverse syrinx width.Methods: Magnetic resonance images of 59 CKCS with CM were retrospectively reviewed and grouped with or without SM. Three-dimensional images were created and volumes of the fossae, brain parenchyma and ventricular system were calculated from which percentages of CCF, CCFP and V were created. If present, syrinx size was measured from its maximal transverse width. The percentages were statistically compared between groups, and correlation between percentages and syrinx dimensions was made.Results: CKCS with SM had significantly higher CCFP (P=0·0001) and V (P=0·0002) to those without but no significant difference in CCF (P=0·925). There was a positive correlation between CCFP and syrinx width (Pearson r=0·437) and ventricle size to syrinx width (Spearman r=0·627).Clinical Significance: A more marked overcrowding of the CCF is associated with SM, which may explain the high incidence of SM in CKCS with CM. The association between ventricle and syrinx dimensions supports the theory that SM development is the result of altered cerebrospinal fluid dynamics. © 2010 British Small Animal Veterinary Association.
Rusbridge C, Greitz D, Iskandar BJ (2006) Syringomyelia: current concepts in pathogenesis, diagnosis, and treatment., J Vet Intern Med 20 (3) pp. 469-479
Syringomyelia is a condition that results in fluid-containing cavities within the parenchyma of the spinal cord as a consequence of altered cerebrospinal fluid dynamics. This review discusses the history and the classification of the disorder, the current theories of pathogenesis, and the advanced imaging modalities used in the diagnosis. The intramedullary pulse pressure theory (a new pathophysiologic concept of syringomyelia) also is presented. In addition, the current understanding of the painful nature of this condition is discussed and the current trends in medical and surgical management are reviewed.
Plessas IN, Rusbridge C, Driver CJ, Chandler KE, Craig A, McGonnell IM, Brodbelt DC, Volk HA (2012) Long-term outcome of Cavalier King Charles spaniel dogs with clinical signs associated with Chiari-like malformation and syringomyelia, Veterinary Record 171 (20)
The disease complex Chiari-like malformation (CM) and syringomyelia (SM) has been associated with the development of neuropathic pain (NeP), and commonly affects Cavalier King Charles spaniels (CKCS). This prospective cohort study followed 48 CKCSs with CM and/or SM and clinical signs suggestive of NeP for a period of 39 (±14.3) months from diagnosis. At the end of the study, 36 dogs were still alive; five dogs died of an unrelated or unknown cause, and seven were euthanased due to severe clinical signs suggestive of NeP. During the follow-up period, the clinical signs of scratching, facial rubbing behaviour, vocalisation and exercise ability were evaluated. Nine out of 48 dogs stopped scratching (P
Rusbridge C, Marioni?Henry K, Volk H (2016) Clinical Features in Border Terrier Dogs with Paroxysmal Involuntary Movements, Movement Disorders Clinical Practice 3 (1) pp. 73-79 Wiley
Abstract Background There have been anecdotal reports of episodic involuntary movements in the Border Terrier dog breed for over a decade. Recently, it has been hypothesized that this condition may be a form of paroxysmal dystonic choreoathetosis. The aim of this study was to characterize the phenomenology and clinical course of this condition and compare it to known human movement disorders. Methods Data were collected retrospectively from clinical cases treated by veterinary neurologists and additional information was collected prospectively with an ad-hoc online survey directed to owners of affected dogs. Results The episodes are characterized by generalized dystonia, tremors, titubation, and, in some cases, autonomic signs, such as salivation and vomiting. The median age at onset of the episodes was 3 years and the interval between clusters of episodes could last several months. Most of the episodes occurred from rest, and 67% of the owners reported that the episodes were associated with a trigger, most often excitement. Some owners reported an improvement after changing their dog's diet. We hypothesize that the Border Terrier attacks represent a form of paroxysmal nonkinesigenic dyskinesia. Conclusions The finding of a dystonia phenotype within an inbred population suggests a genetic predisposition, and elucidating the genetic cause could facilitate improved understanding of dystonia. This genetic predisposition and the effect of treatment with anticonvulsant drugs and dietary changes on the severity of the paroxysms warrant further investigation on this condition.
Shaw TA, McGonnell IM, Driver CJ, Rusbridge C, Volk HA (2013) Caudal cranial fossa partitioning in Cavalier King Charles spaniels, Veterinary Record 172 (13)
Kent A, Constantino-Casas F, Rusbridge C, Corcoran B, Carter M, Ledger T, Watson P (2016) Prevalence of pancreatic, hepatic andrenal microscopic lesions in post-mortem samples from cavalier King Charles spaniels, JOURNAL OF SMALL ANIMAL PRACTICE 57 (4) pp. 188-193 WILEY-BLACKWELL
De Risio L, Bhatti S, Munana K, Penderis J, Stein V, Tipold A, Berendt M, Farqhuar R, Fischer A, Long S, Mandigers P, Matiasek K, Packer R, Pakozdy A, Patterson N, Platt S, Podell M, Potschka H, Pumarola Batlle M, Rusbridge C, Volk H (2015) International veterinary epilepsy task force consensus proposal: diagnostic approach to epilepsy in dogs, BMC VETERINARY RESEARCH 11 ARTN 148 BIOMED CENTRAL LTD
Cherubini GB, Platt SR, Anderson TJ, Rusbridge C, Lorenzo V, Mantis P, Cappello R (2006) Characteristics of magnetic resonance images of granulomatous meningoencephalomyelitis in 11 dogs., Vet Rec 159 (4) pp. 110-115
The characteristics of magnetic resonance imaging (mri) of the brains and spinal cords of 11 dogs with histologically confirmed granulomatous meningoencephalomyelitis (gme) were determined. The lesions were in the brain of eight of the dogs, in the brain and spinal cord of two, and in the spinal cord alone in one dog. A single lesion was present in four of the dogs and multiple lesions were found in six. In one dog with intracranial signs, no visible lesions could be detected on mri. No meningeal enhancement was detected in T1-weighted images post-contrast, or in fluid attenuation inversion recovery (flair) images, but there were histological lesions in the meninges in nine of the dogs. The T2-weighted images and flair sequences were characterised in all cases by hyperintensity, whereas the signal intensity of the lesions on T1-weighted images was variable. After the administration of paramagnetic contrast, some of the lesions showed no enhancement, but others showed marked patterns of enhancement. The lesions in 10 of the dogs were easily identifiable by mri and the images had several unifying characteristics, but they could not be considered disease-specific.
Costanzo C, Garosi LS, Glass EN, Rusbridge C, Stalin CE, Volk HA (2011) Brain abscess in seven cats due to a bite wound: MRI findings, surgical management and outcome, Journal of Feline Medicine and Surgery 13 (9) pp. 672-680
Presentation and lesion localisation: Seven adult domestic shorthair cats were presented with a 1- to 6-day history of progressive neurological signs. A focal skin puncture and subcutaneous swelling over the dorsal part of the head were detected on physical examination. Neurological examination indicated lesion(s) in the right forebrain in four cats, multifocal forebrain in one cat, left forebrain in one cat, and multifocal forebrain and brainstem in the remaining cat. In all cats, magnetic resonance imaging revealed a space-occupying forebrain lesion causing a severe mass effect on adjacent brain parenchyma. Clinical approach and outcome: All cats were managed with a combination of medical and surgical treatment. At surgery a small penetrating calvarial fracture was detected in all cats, and a tooth fragment was found within the content of the abscess in two cats. The combination of surgical intervention, intensive care and intravenous antimicrobials led to a return to normal neurological function in five cats. Practical relevance: As this series of cases indicates, successful resolution of a brain abscess due to a bite injury depends on early recognition and combined used of antimicrobials and surgical intervention. A particular aim of surgery is to remove any skull and foreign body (tooth) fragments that may represent a continuing focus of infection. © 2011 ISFM and AAFP.
Driver CJ, Rusbridge C, McGonnell IM, Volk HA (2010) Morphometric assessment of cranial volumes in age-matched Cavalier King Charles spaniels with and without syringomyelia, Veterinary Record 167 (25) pp. 978-979
Rusbridge C, Heath S (2015) Feline Orofacial Pain Syndrome in Feline Behavioral Health and Welfare, pp. 213-226 Elsevier Health Sciences
Ilona Rodan, Sarah Heath. 10. 11. 12. 13. 14. 15. 16. 6. 7. 8. 9. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. PART The Cat in the Veterinary Practice Physiologic and Diagnostic. (MEMO) in the management of cats with idiopathic cystitis.
Lujan Feliu-Pascual A, Shelton GD, Targett MP, Long SN, Comerford EJ, McMillan C, Davies D, Rusbridge C, Mellor D, Chang KC, Anderson TJ (2006) Erratum: Inherited myopathy of great Danes (Journal of Small Animal Practice (2006) 47, (249-254)), Journal of Small Animal Practice 47 (6)
Mandigers P, Rusbridge C (2009) Op Chiari lijkende malformatieSyringomyelie bij de Cavalier King Charles Spaniel, Tijdschrift voor Diergeneeskunde 134 (18) pp. 746-750
This article, which is based on the PhD thesis of Clare Rusbridge, is a review of chiari-like malformation and syringomyelia in the Cavalier King Charles Spaniel. The abnormality is becoming more common among dwarf breeds and brachychepalic breeds. The nature, prevalence, and treatment of the disease are described, as is current knowledge on its heritability in the Cavalier King Charles Spaniel.
Hu HZ, Rusbridge C, Constantino-Casas F, Jeffery N (2012) Histopathological Investigation of Syringomyelia in the Cavalier King Charles Spaniel, Journal of Comparative Pathology 146 (2-3) pp. 192-201
Syringomyelia (SM) in Cavalier King Charles spaniels (CKCSs) is identified commonly on magnetic resonance images and is sometimes associated with clinical signs of pain and cervical hyperaesthesia. However, the mechanism by which SM develops in this breed has not been fully elucidated and the associated effects on spinal cord structure have not been reported previously. The aims of this study were to describe changes found in the spinal cord of CKCSs, to compare findings between symptomatic and asymptomatic dogs and to determine whether syrinx formation was associated with tissue destruction. Anomalies of the central canal were found in all specimens and many dogs had grossly visible fluid-filled cavities within the spinal cord. Prominent microscopical findings were spongy degenerative changes associated with neuronal necrosis and Wallerian degeneration. The ependyma was discontinuous in many specimens, notably in symptomatic individuals, and there was evidence of angiogenesis and fibrous tissue proliferation around blood vessels adjacent to syrinx cavities. Compared with two different samples of the normal dog population, dogs with syrinxes had significantly less grey matter, although this decrease was associated with generalized loss of spinal cord area. Therefore, SM is associated with degenerative changes in the spinal cord and may develop through primary disruption of ependymal integrity followed by vascular hypertrophy and proliferation. Glial and fibrous proliferation appears to be associated with expression of clinical signs. © 2011 Elsevier Ltd.
Rutherford L, Wessmann A, Rusbridge C, McGonnell IM, Abeyesinghe S, Burn C, Volk HA (2012) Questionnaire-based behaviour analysis of Cavalier King Charles spaniels with neuropathic pain due to Chiari-like malformation and syringomyelia, Veterinary Journal 194 (3) pp. 294-298
Chiari-like malformation (CM)/syringomyelia (SM) is a disease complex recognised in Cavalier King Charles spaniels (CKCSs) that can lead to neuropathic pain (NeP). In humans, NeP is associated with anxiety, depression and reduced quality of life (QoL). In this study, databases of three specialist veterinary centres were searched and CKCS breed societies and health forums were contacted to identify CKCS with an imaging diagnosis of CM/SM. Owners completed questionnaires on behaviour, signalment, general health status, NeP and QoL. Data were analysed from 122 dogs out of 564 questionnaires completed, after incomplete questionnaires and data from dogs that had other potentially debilitating disease processes were excluded. NeP severity score was significantly and positively correlated with 'stranger-directed' fear (rS=0.28), non-social fear (rS=0.34), 'separation-related' behaviour (rS=0.38), attachment behaviour (rS=0.24), excitability (rS=0.21) and proxy for pain sensation (rS=0.29). Increased NeP was also significantly associated with decreased QoL (rS=0.47), ability to settle (rS=0.26) and willingness to exercise (rS=0.50). Severity of NeP was positively associated with certain fear-associated behaviour and with decreased owner-perceived QoL. Thus, neurobehavioural changes should be considered in the management of NeP in CKCS with CM/SM. © 2012 Elsevier Ltd.
Rusbridge C, Knowler SP, Pieterse L, McFadyen AK (2009) Chiari-like malformation in the griffon bruxellois, Journal of Small Animal Practice 50 (8) pp. 386-393
Objectives: This study describes Chiari-like malformation and syringomyelia in the Griffon Bruxellois and establishes if skull radiographs are useful for disease prediction. Methods: Magnetic resonance imaging from 56 Griffon Bruxellois dogs was assessed for Chiari-like malformation and cerebrospinal fluid pathway abnormalities. Skull radiographs were obtained in 33 dogs. Two rostrocaudal and two ventrodorsal measurements were made, and ratios of one length to another were compared. Results: In this selected sample, 60·7 per cent had Chiari-like malformation. Syringomyelia occurred with and without Chiari-like malformation (37·5 and 8·9 per cent study population, respectively). The radiographic study demonstrated that one measurement ratio could be used to predict Chiari-like malformation (sensitivity of 87 per cent and specificity of 78 per cent) and that there were significant interaction factors between sex and syringomyelia for two measurement ratios. Clinical Significance: The study suggests that Chiari-like malformation is characterised by a shortening of the basicranium and supra-occipital bone with a compensatory lengthening of the cranial vault, especially the parietal bone. We described a simple radiographic technique, which may be useful as a screening test until a more definite genetic test for Chiari-like malformation is available. © 2009 British Small Animal Veterinary Association.
Kennedy LJ, Quarmby S, Happ GM, Barnes A, Ramsey IK, Dixon RM, Catchpole B, Rusbridge C, Graham PA, Hillbertz NS, Roethel C, Dodds WJ, Carmichael NG, Ollier WE (2006) Association of canine hypothyroidism with a common major histocompatibility complex DLA class II allele., Tissue Antigens 68 (1) pp. 82-86
Dogs exhibit a range of immune-mediated conditions including a lymphocytic thyroiditis which has many similarities to Hashimoto's thyroiditis in man. We have recently reported an association in Doberman Pinschers between canine hypothyroidism and a rare DLA class II haplotype that contains the DLA-DQA1*00101 allele. We now report a further series of 173 hypothyroid dogs in a range of breeds where a significant association with DLA-DQA1*00101 is shown.
Cherubini GB, Rusbridge C, Singh BP, Schoeniger S, Mahoney P (2007) Rostral cerebellar arterial infarct in two cats., J Feline Med Surg 9 (3) pp. 246-253
A 10-year-old female neutered domestic shorthair (DSH) cat and a 6-year-old female neutered Siamese cat were presented following a peracute onset of decerebellate rigidity and a cerebellar vestibular syndrome, respectively. In both cats, physical examination and routine blood tests were unremarkable, as was routine analysis of cerebrospinal fluid obtained from the DSH cat. Based on the magnetic resonance imaging (MRI) features - focal wedge-shaped lesion in the cerebellum characterised by hyperintensity in T2-weighted, T2( *)-gradient echo and fluid attenuated inversion recovery (FLAIR) images - a presumptive diagnosis of cerebellar infarct was made in both cases. In the DSH cat, the post-mortem examination confirmed the diagnosis of cerebellar infarct and additionally found acute renal infarcts and a pulmonary neoplasia. In the Siamese cat, ultrasonographic evaluation of the heart revealed a probable low-grade chronic valvular endocarditis which was thought to be a potential source of thromboembolism. This paper describes the first two cases - one confirmed and the other suspected - of cerebellar infarct in the cat. The in vivo potential diagnostic value of the MRI study is highlighted. Cerebellar infarcts should be included in the differential diagnosis of cat with a peracute onset of cerebellar signs regardless of the severity of neurological deficits.
Lemay P, Knowler SP, Bouasker S, Nédélec Y, Platt S, Freeman C, Child G, Barreiro LB, Rouleau GA, Rusbridge C, Kibar Z (2014) Quantitative trait loci (QTL) study identifies novel genomic regions associated to Chiari-like malformation in Griffon Bruxellois dogs., PLoS One 9 (4)
Chiari-like malformation (CM) is a developmental abnormality of the craniocervical junction that is common in the Griffon Bruxellois (GB) breed with an estimated prevalence of 65%. This disease is characterized by overcrowding of the neural parenchyma at the craniocervical junction and disturbance of cerebrospinal fluid (CSF) flow. The most common clinical sign is pain either as a direct consequence of CM or neuropathic pain as a consequence of secondary syringomyelia. The etiology of CM remains unknown but genetic factors play an important role. To investigate the genetic complexity of the disease, a quantitative trait locus (QTL) approach was adopted. A total of 14 quantitative skull and atlas measurements were taken and were tested for association to CM. Six traits were found to be associated to CM and were subjected to a whole-genome association study using the Illumina canine high density bead chip in 74 GB dogs (50 affected and 24 controls). Linear and mixed regression analyses identified associated single nucleotide polymorphisms (SNPs) on 5 Canis Familiaris Autosomes (CFAs): CFA2, CFA9, CFA12, CFA14 and CFA24. A reconstructed haplotype of 0.53 Mb on CFA2 strongly associated to the height of the cranial fossa (diameter F) and an haplotype of 2.5 Mb on CFA14 associated to both the height of the rostral part of the caudal cranial fossa (AE) and the height of the brain (FG) were significantly associated to CM after 10 000 permutations strengthening their candidacy for this disease (P
=
0.0421, P
=
0.0094 respectively). The CFA2 QTL harbours the Sall-1 gene which is an excellent candidate since its orthologue in humans is mutated in Townes-Brocks syndrome which has previously been associated to Chiari malformation I. Our study demonstrates the implication of multiple traits in the etiology of CM and has successfully identified two new QTL associated to CM and a potential candidate gene.
Rusbridge C, Carruthers H, Dubé MP, Holmes M, Jeffery ND (2007) Syringomyelia in cavalier King Charles spaniels: the relationship between syrinx dimensions and pain., J Small Anim Pract 48 (8) pp. 432-436
OBJECTIVES: This study was designed to test the hypothesis that pain associated with syringomyelia in dogs is dependent upon size and involvement of the dorsal part of the spinal cord. METHODS: Masked observers determined syrinx dimensions and precise location within the spinal cord on magnetic resonance images of 55 cavalier King Charles spaniels with syringomyelia. After removal of masking, syrinx size and location were compared between the cohorts of dogs that exhibited pain with those that did not. RESULTS: Maximum syrinx width was the strongest predictor of pain, scratching behaviour and scoliosis in dogs with syringomyelia. Both pain and syrinx size were positively correlated with syrinxes located in the dorsal half of the spinal cord. CLINICAL SIGNIFICANCE: Large syrinxes associated with damage to the dorsal part of the spinal cord are associated with persistent pain suggesting that the pain behaviour expressed by this group of patients is likely to be "neuropathic pain," resulting from disordered neural processing in the damaged dorsal horn. As such it is likely that conventional analgesic medication may be ineffective.
Shaw TA, McGonnell IM, Driver CJ, Rusbridge C, Volk HA (2012) Increase in cerebellar volume in Cavalier King Charles Spaniels with Chiari-like malformation and its role in the development of syringomyelia., PLoS One 7 (4)
Previous research in Cavalier King Charles Spaniels (CKCS) has found that Chiari-like malformation and syringomyelia (CM/SM) are associated with a volume mismatch between the caudal cranial fossa (CCF) and the brain parenchyma contained within. The objectives of this study were to i) compare cerebellar volume in CKCS (a "high risk' group which frequently develops CM/SM), small breed dogs (medium risk--occasionally develop CM/SM), and Labradors (low risk--CM/SM not reported); ii) evaluate a possible association between increased cerebellar volume and CM/SM in CKCS; iii) investigate the relationship between increased cerebellar volume and crowding of the cerebellum in the caudal part of the CCF (i.e. the region of the foramen magnum). Volumes of three-dimensional, magnetic resonance imaging derived models of the CCF and cerebellum were obtained from 75 CKCS, 44 small breed dogs, and 31 Labradors. As SM is thought to be a late onset disease process, two subgroups were formed for comparison: 18 CKCS younger than 2 years with SM (CM/SM group) and 13 CKCS older than 5 years without SM (CM group). Relative cerebellar volume was defined as the volume of the cerebellum divided by the total volume of brain parenchyma. Our results show that the CKCS has a relatively larger cerebellum than small breed dogs and Labradors and provide evidence that increased cerebellar volume in CKCS is associated with crowding of cerebellum in the caudal part of the CCF. In CKCS there is an association between increased cerebellar volume and SM. These findings have implications for the understanding of the pathological mechanisms of CM/SM, and support the hypothesis that it is a multifactorial disease process governed by increased cerebellar volume and failure of the CCF to reach a commensurate size.
Carruthers H, Rusbridge C, Dubé MP, Holmes M, Jeffery N (2009) Association between cervical and intracranial dimensions and syringomyelia in the cavalier king charles spaniel, Journal of Small Animal Practice 50 (8) pp. 394-398
Objectives: To investigate the possible association between caudal fossa area and cervical vertebral dimensions and the presence of syringomyelia in cavalier King Charles spaniels. Methods: From magnetic resonance imaging scans of 78 cavalier King Charles spaniels, measurements were made of the widest vertical spinal width at C1/C2, C2, C2/C3 and C3; angulation of the C2/C3 spine; and estimated caudal fossa area. A correlation between these measurements and syringomyelia was sought. Results: A total of 59 dogs with and 19 without syringomyelia were compared. Older dogs had a significantly higher incidence of syringo-myelia. No difference in incidence was noted between genders. There was no significant difference in vertebral canal width at C1/C2 and C2, or angulation of C2/C3 between syringomyelia and non-syringomyelia groups. The width of the canal at C2/C3 and C3 was significantly increased in syringomyelia dogs. There was no significant difference in the caudal fossa area between groups. Clinical Significance: Although syringomyelia was shown to be more prevalent in older dogs, the age beyond which dogs were considered at greater risk was not deducible from the dataset. The association identified between wider spinal canal at C3, and C2/C3 and syringomyelia presence is of questionable clinical significance, as the difference between syringomyelia and non-syringomyelia groups is too small to be measured in a clinical setting. © 2009 British Small Animal Veterinary Association.
Rusbridge C, Heath S (2015) Feline Orofacial Pain Syndrome, In: Rodan I, Heath S (eds.), Feline Behavioral Health and Welfare 16 pp. 213-227 Saunders
Chandler K, Volk H, Rusbridge C, Jeffery N (2008) Syringomyelia in cavalier King Charles spaniels., Vet Rec 162 (10)
Flint G, Rusbridge C (2014) Historical Vignettes, In: Flint G, Rusbridge C (eds.), Syringomyelia: A Disorder of CSF Circulation 23 pp. 329-335 Springer
A patient once remarked about how a certain individual, by the name of Arnold Chiari, had affected her and her family?s life. This serves to remind us that it might sometimes be helpful if doctors could find time to explain to their patients not only the meaning of the term Arnold-Chiari malformation but also its origins.
Bhatti SF, Vanhaesebrouck AE, Van Soens I, Martlé VA, Polis IE, Rusbridge C, Van Ham LM (2011) Myokymia and neuromyotonia in 37 Jack Russell terriers, Veterinary Journal 189 (3) pp. 284-288
The clinical and clinicopathological characteristics, treatment and outcome of vermicular muscle contractions (myokymia) and generalized muscle stiffness (neuromyotonia) in 37 Jack Russell terriers were evaluated retrospectively. Thirty dogs were affected by both disorders, whereas seven were presented with myokymia and never developed neuromyotonia. Clinical signs started at the mean age of 8. months. Except for signs of myokymia and neuromyotonia, clinical and neurological examination was normal in all dogs. Thirty dogs demonstrated typical signs of hereditary ataxia.Changes in serum chemistry included increased creatine kinase, aspartate aminotransferase and alanine aminotransferase concentrations. Electromyographic abnormalities, especially in muscles showing macroscopically visible myokymia, consisted of semirhythmic bursts of doublet, triplet, or multiplet discharges of a single motor unit. The amplitudes varied between 80 ¼V and 1. mV and occurred with an interburst frequency between 10 and 40. Hz and an intraburst frequency between 150 and 280. Hz.Most dogs were treated with a sodium channel blocker with variable results. Seven dogs died (most likely because of hyperthermia) or were euthanased during a neuromyotonic attack; 15 dogs were euthanased due to worsening of clinical signs, or lack of or no long-lasting effect of medication, and three were euthanased for unknown or unrelated reasons. Nine dogs were lost to follow-up and three were still alive 5-10.5. years after the start of clinical signs. In conclusion, young Jack Russell terriers with myokymia and neuromyotonia should undergo a complete blood and electrophysiological examination. Long-term prognosis is not favourable. © 2010 Elsevier Ltd.
Hu HZ, Rusbridge C, Constantino-Casas F, Jeffery N (2012) Distribution of substance P and calcitonin gene-related peptide in the spinal cord of Cavalier King Charles Spaniels affected by symptomatic syringomyelia, Research in Veterinary Science 93 (1) pp. 318-320
The causes of clinical signs associated with syringomyelia in the Cavalier King Charles Spaniel (CKCS) are incompletely understood. In this study we compared expression of two pain-related neuropeptides: substance P (SP) and calcitonin gene related peptide (CGRP), in the spinal cord dorsal horn of normal dogs with that in CKCS with and without clinical signs of syringomyelia. There was a decrease in expression of both peptides in CKCS with 'symptomatic' syringomyelia that was also associated with significant asymmetry in SP-I and similar, though non-significant, asymmetry in CGRP-I compared with other groups. The asymmetric distribution of these pain-related peptides may be a consequence of syrinx-associated damage to grey matter but may also play a role in generation of pain. © 2011 Elsevier Ltd.
Rusbridge C (2014) Veterinary Aspects, In: Flint G, Rusbridge C (eds.), Syringomyelia: A Disorder of CSF Circulation (14) 14 pp. 209-230 Springer-Verlag Berlin Heidelberg
Syringomyelia is an increasingly common diagnosis in veterinary medicine, especially in toy breed dogs where selections for small size and brachycephalic head shape are contributing factors. The most common cause is a condition analogous to Chiari I malformation in humans. This chapter details the pathophysiology, clinical signs, medical and surgical management, progression and prognosis of the canine condition. As a naturally occurring model of both syringomyelia and central neuropathic pain, observations that may have relevance to understanding of the pathophysiology of Chiari malformation and syringomyelia in humans are discussed. Finally, current knowledge of genetic factors and breeding advice is reviewed.
Packer RM, Berendt M, Bhatti S, Charalambous M, Cizinauskas S, De Risio L, Farquhar R, Hampel R, Hill M, Mandigers PJ, Pakozdy A, Preston SM, Rusbridge C, Stein VM, Taylor-Brown F, Tipold A, Volk HA (2015) Inter-observer agreement of canine and feline paroxysmal event semiology and classification by veterinary neurology specialists and non-specialists., BMC Vet Res 11 (1)
Advances in mobile technology mean vets are now commonly presented with videos of paroxysmal events by clients, but the consistency of the interpretation of these videos has not been investigated. The objective of this study was to investigate the level of agreement between vets (both neurology specialists and non-specialists) on the description and classification of videos depicting paroxysmal events, without knowing any results of diagnostic workup. An online questionnaire study was conducted, where participants watched 100 videos of dogs and cats exhibiting paroxysmal events and answered questions regarding: epileptic seizure presence (yes/no), seizure type, consciousness status, and the presence of motor, autonomic and neurobehavioural signs. Agreement statistics (percentage agreement and kappa) calculated for each variable, with prevalence indices calculated to aid their interpretation.
McGuinness SJ, Friend EJ, Knowler SP, Jeffery ND, Rusbridge C (2013) Progression of otitis media with effusion in the Cavalier King Charles spaniel, Veterinary Record 172 (12)
Rusbridge C, Jeffery ND (2008) Pathophysiology and treatment of neuropathic pain associated with syringomyelia., Vet J 175 (2) pp. 164-172
The pain behaviour expressed by dogs with syringomyelia suggests that they experience neuropathic pain, probably due to disordered neural processing in the damaged dorsal horn. As such it is likely that conventional analgesic medication will be ineffective. In this review, physiological and pathological pain processing through the dorsal horn is summarised and mechanisms by which syringomyelia could result in a persistent pain state are discussed. Finally, current knowledge regarding treatment of Chiari malformation and syringomyelia is reviewed and possible drugs which may give improved pain relief in affected dogs are discussed.
Driver CJ, Volk HA, Rusbridge C, Van Ham LM (2013) An update on the pathogenesis of syringomyelia secondary to Chiari-like malformations in dogs, Veterinary Journal 198 (3) pp. 551-559
Syringomyelia (SM) is a spinal cord disease that can cause neuropathic pain in dogs. The pathogenesis of SM secondary to Chiari-like malformation (CM) has been the focus of intense research in recent years. The gulf in our understanding of CM/SM in dogs relative to the analogous human condition has progressively narrowed. CM is primarily a disease of abnormal geometric morphometry affecting the caudal cranial fossa and the brain parenchyma contained within it. This review describes how advanced imaging techniques have revealed a series of morphometric abnormalities associated with CM/SM. The series is presented in a logical order to help describe the pathogenesis of CM and the subsequent formation of syringes, with particular reference to the concepts of craniospinal compliance and cerebrospinal fluid pulse pressure timing. © 2013 Elsevier Ltd.
Potschka H, Fischer A, Loescher W, Patterson N, Bhatti S, Berendt M, De Risio L, Farquhar R, Long S, Mandigers P, Matiasek K, Munana K, Pakozdy A, Penderis J, Platt S, Podell M, Rusbridge C, Stein V, Tipold A, Volk H (2015) International veterinary epilepsy task force consensus proposal: outcome of therapeutic interventions in canine and feline epilepsy, BMC VETERINARY RESEARCH 11 ARTN 177 BIOMED CENTRAL LTD
Bhatti S, De Risio L, Munana K, Penderis J, Stein V, Tipold A, Berendt M, Farquhar R, Fischer A, Long S, Loescher W, Mandigers P, Matiasek K, Pakozdy A, Patterson E, Platt S, Podell M, Potschka H, Rusbridge C, Volk H (2015) International Veterinary Epilepsy Task Force consensus proposal: medical treatment of canine epilepsy in Europe, BMC VETERINARY RESEARCH 11 ARTN 176 BIOMED CENTRAL LTD
Rusbridge C, Dewey C (2008) Treatment of Chiari-like malformation and Syringomyelia, In: Bonagura J, Twedt D (eds.), Kirk's Current Veterinary Therapy XIV (240) 240 pp. 1102-1107 Saunders
Berendt M, Farquhar R, Mandigers P, Pakozdy A, Bhatti S, De Risio L, Fischer A, Long S, Matiasek K, Munana K, Patterson E, Penderis J, Platt S, Podell M, Potschka H, Pumarola M, Rusbridge C, Stein V, Tipold A, Volk H (2015) International veterinary epilepsy task force consensus report on epilepsy definition, classification and terminology in companion animals, BMC VETERINARY RESEARCH 11 ARTN 182 BIOMED CENTRAL LTD
Cross HR, Cappello R, Rusbridge C (2009) Comparison of cerebral cranium volumes between cavalier king charles spaniels with chiari-like malformation, small breed dogs and labradors, Journal of Small Animal Practice 50 (8) pp. 399-405
Objectives: To ascertain whether cavalier King Charles spaniels (CKCSs) have a proportionately smaller caudal fossa compared with other small dogs and with Labradors. To evaluate if cerebellar herniation in CKCS correlates with caudal fossa volume. Methods: In this retrospective study, three-dimensional images were created from magnetic resonance imaging brain series of 117 dogs (split into three groups: CKCS, Labradors and small breeds) from which the volumes of the fossae and brain parenchyma were calculated. These volumes were transformed into percentages of total cranial cavity and parenchyma volumes, respectively. The percentages were statistically compared among the groups. The percentage of herniated cerebellum in the CKCS was compared using linear regression with the caudal fossa and parenchyma percentages. Results: Cavalier King Charles spaniels had a proportionately smaller caudal fossa compared with Labradors (P=0·002) but not to small breeds (P=0·103). Their caudal fossa parenchyma was proportionately the same volume as Labradors (P=0·976) but greater than small breeds (P=0·005). No relationship was found for the per cent of cerebellum herniated. Clinical Significance: The results support mesoderm insufficiency or craniosynostosis as the pathogenesis of Chiari-like malformation (CM) in CKCS. It presents evidence for overcrowding of the caudal fossa due to a mismatch of brain parenchyma and fossa volumes as to why CKCS and not other small dogs are affected. © 2009 British Small Animal Veterinary Association.
Rusbridge C (2014) Canine idiopathic epilepsy, IN PRACTICE 36 (Supp 1) pp. 17-23 BRITISH VETERINARY ASSOC
Canine idiopathic epilepsy has an estimated prevalence of 0.62 per cent in primary veterinary practice (Kearsley-Fleet and others 2013) and as such is one of the most common chronic neurological diseases. Descriptions of ?epilepsy of unknown origin . . . where no symptom characteristic of any other condition has as yet presented? can be found in early veterinary textbooks (Kirk 1922) and although our knowledge is now considerably greater, and we are no longer treating it with arsenic, we are still a long way from preventing or curing this enigmatic disease. This article describes the diagnosis, management and considerations to take when dealing with this condition.
Rusbridge C, Long S, Jovanovik J, Milne M, Berendt M, Bhatti S, De Risio L, Farqhuar R, Fischer A, Matiasek K, Munana K, Patterson E, Pakozdy A, Penderis J, Platt S, Podell M, Potschka H, Stein V, Tipold A, Volk H (2015) International Veterinary Epilepsy Task Force recommendations for a veterinary epilepsy-specific MRI protocol, BMC VETERINARY RESEARCH 11 ARTN 194 BIOMED CENTRAL LTD
Lujan Feliu-Pascual A, Shelton GD, Targett MP, Long SN, Comerford EJ, McMillan C, Davies D, Rusbridge C, Mellor D, Chang KC, Anderson TJ (2006) Inherited myopathy of great Danes., J Small Anim Pract 47 (5) pp. 249-254
A hereditary, non-inflammatory myopathy occurring in young great Danes with distinctive histological features in muscle biopsy specimens is reviewed. Onset of clinical signs is usually before one year of age and both sexes are affected. Clinical signs are characterised by exercise intolerance, muscle wasting, and an exercise-induced tremor. Although most affected dogs have a severe form of the disease, occasional dogs may have a less pronounced form and survive into adulthood with an acceptable quality of life. Litters containing affected puppies are born to clinically unaffected parents, and an autosomal recessive pattern of inheritance is likely. All recorded cases have had fawn or brindle coat coloration. Elevated serum creatinine kinase concentrations and spontaneous electrical activity in skeletal muscles are frequently found. While originally reported (Targett and others 1994) as a central core myopathy in this breed, the histochemical characteristics of the distinct cytoarchitectural structures differ from those of the well-characterised central core myopathy in human beings. In fact, these structures differ from any known myopathy in human beings and likely represents a unique non-inflammatory myopathy affecting dogs. Until this myopathy is characterised further, the name inherited myopathy in great Danes is suggested.
Rusbridge C (2013) Choosing the right drug 1. Anticonvulsants used for first-line therapy, In Practice 35 (3) pp. 106-113
This article aims to give the general practitioner a step by step approach to first-line medical management of epilepsy in both cats and dogs. The licensed drugs, bromide and phenobarbital, are discussed in detail with particular reference to the common problems that might be observed. A second article in this two-part series, to be published in a subsequent issue of In Practice, will discuss second-line medical management of epilepsy.
Rusbridge C, Nicholas N, Addicott D (2011) Breed-specific diseases: Polymyositis and DNA collection in the Hungarian vizsla dog, Veterinary Record 168 (3) pp. 85-86
Cappello R, Rusbridge C, Chiari-Like Malformation and Syringomyelia Working Group (2007) Report from the Chiari-Like Malformation and Syringomyelia Working Group round table., Vet Surg 36 (5) pp. 509-512
Parker JE, Knowler SP, Rusbridge C, Noorman E, Jeffery ND (2011) Prevalence of asymptomatic syringomyelia in Cavalier King Charles spaniels, Veterinary Record 168 (25)
The prevalence of syringomyelia was investigated in a sample population of 555 Cavalier King Charles spaniels. All dogs, which were declared by their owners to be showing no clinical signs of syringomyelia, underwent MRI to determine the presence or absence of the condition. Data were analysed by logistic regression to determine the effects of sex and age on the prevalence of syringomyelia. Only increased age was found to have a significant effect. The prevalence of syringomyelia was 25 per cent in dogs aged 12 months, increasing to a peak of 70 per cent in dogs aged 72 months or more.
Hesselink J, Rusbridge C (2014) Pain Management, In: Flint G, Rusbridge C (eds.), Syringomyelia: A Disorder of CSF Circulation (16) 16 pp. 237-259 Springer-Verlag Berlin Heidelberg
In this chapter, our current understanding of the mechanisms causing neuropathic pain and the nonsurgical therapy of syringomyelia are reviewed. Traditional pharmacological therapies such as tricyclic antidepressants, serotonin antagonist and reuptake inhibitors, antiepileptic drugs, opioids and NMDA receptor antagonists are detained, together with novel drug therapies such as cannabis, endocannabinoids and naltrexone. Management strategies for central neuropathic pain are suggested, including combination therapy, topical analgesics and intrathecal infusions. Limitations of therapy are discussed, together with likely future directions for treatment. Non-pharmacological treatments, such as acupuncture, complementary medicine, cognitive therapy and neurostimulation, are also considered.
Thomsen B, Garosi L, Skerritt G, Rusbridge C, Sparrow T, Berendt M, Gredal H (2016) Neurological signs in 23 dogs with suspected rostral cerebellar ischaemic stroke, Acta Veterinaria Scandinavica 58 (40) ARTN 40 BioMed Central
Background: In dogs with ischaemic stroke, a very common site of infarction is the cerebellum. The aim of this study was to characterise neurological signs in relation to infarct topography in dogs with suspected cerebellar ischaemic stroke and to report short-term outcome confined to the hospitalisation period. A retrospective multicentre study of dogs with suspected cerebellar ischaemic stroke examined from 2010?2015 at five veterinary referral hospitals was performed. Findings from clinical, neurological, and paraclinical investigations including magnetic resonance imaging were assessed. Results: Twenty-three dogs, 13 females and 10 males with a median age of 8 years and 8 months, were included in the study. The Cavalier King Charles Spaniel (n = 9) was a commonly represented breed. All ischaemic strokes were located to the vascular territory of the rostral cerebellar artery including four extensive and 19 limited occlusions. The most prominent neurological deficits were gait abnormalities (ataxia with hypermetria n = 11, ataxia without hypermetria n = 4, non-ambulatory n = 6), head tilt (n = 13), nystagmus (n = 8), decreased menace response (n = 7), postural reaction deficits (n = 7), and proprioceptive deficits (n = 5). Neurological signs appeared irrespective of the infarct being classified as extensive or limited. All dogs survived and were discharged within 1?10 days of hospitalisation. Conclusions: Dogs affected by rostral cerebellar ischaemic stroke typically present with a collection of neurological deficits characterised by ataxia, head tilt, and nystagmus irrespective of the specific cerebellar infarct topography. In dogs with peracute to acute onset of these neurological deficits, cerebellar ischaemic stroke should be considered an important differential diagnosis, and neuroimaging investigations are indicated. Although dogs are often severely compromised at presentation, short-term prognosis is excellent and rapid clinical improvement may be observed within the first week following the ischaemic stroke.
Knowler SP, Cross C, Griffiths S, McFadyen A, Jovanovik J, Tauro A, Kibar Z, Driver K, La Ragione RM, Rusbridge C (2017) Use of Morphometric Mapping to Characterise Symptomatic Chiari-Like Malformation, Secondary Syringomyelia and Associated Brachycephaly in the Cavalier King Charles Spaniel, PLoS One 12 (1) e0170315 Public Library of Science (PLoS)
Objectives To 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. Methods This 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. Results Fourteen 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
Knowler S, Kiviranta A, McFadyen A, Jokinen T, La Ragione R, Rusbridge C (2017) Craniometric Analysis of the Hindbrain and Craniocervical Junction of Chihuahua, Affenpinscher and Cavalier King Charles Spaniel Dogs With and Without Syringomyelia Secondary to Chiari-Like Malformation, PLoS One 12 (1) e0169898 Public Library of Science (PLoS)
Objectives:To characterize and compare the phenotypic variables of the hindbrain and craniocervical junction associated with syringomyelia (SM) in the Chihuahua, Affenpinscher and Cavalier King Charles Spaniel (CKCS). Method Analysis of 273 T1-weighted mid-sagittal DICOM sequences of the hindbrain and craniocervical junction from 99 Chihuahuas, 42 Affenpinschers and 132 CKCSs. The study compared 22 morphometric features (11 lines, eight angles and three ratios) of dogs with and without SM using refined techniques based on previous studies of the Griffon Bruxellois (GB) using Discriminant Function Analysis and ANOVA with post-hoc corrections. Results The analysis identified 14/22 significant traits for SM in the three dog breeds, five of which were identical to those reported for the GB and suggest inclusion of a common aetiology. One ratio, caudal fossa height to the length of the skull base extended to an imaginary point of alignment between the atlas and supraoccipital bones, was common to all three breeds (p values 0.029 to
Hajek I, Kettner F, Simerdova V, Rusbridge C, Wang P, Minassian B, Palus V (2016) NHLRC1 repeat expansion in two beagles with Lafora disease, Journal of Small Animal Practice 57 (11) pp. 650-652 Wiley
Lafora disease is a fatal genetic disorder characterised by neurotoxic deposits of malformed insoluble glycogen. In humans it is caused by mutation in the EPM2A or NHLRC1 genes. There is a known mutation in miniature wirehaired dachshunds which has not been documented in other dog breeds, including beagles, in which the disease is relatively commonly reported. This case report describes the causative defect in two affected beagles, namely the same massive expansion as in miniature wirehaired dachshunds of a 12-nucleotide repeat sequence that is unique to the canine NHLRC1 gene. This is the first mutation described in beagles with Lafora disease, and so far the only Lafora disease genetic variant in dogs.
Lazzerini K, Gutierrez-Quintana R, Jose-Lopez R, McConnell F, Goncalves R, McMurrough J, De Decker S, Muir C, Priestnall S, Mari L, Stabile F, De Risio L, Loeffler C, Tauro A, Rusbridge C, Rodenas S, Anor S, de la Fuente C, Fischer A, Bruehschwein A, Penderis J, Guevar J (2017) Clinical Features, Imaging Characteristics, and Long-term Outcome of Dogs with Cranial Meningocele or Meningoencephalocele., Journal of Veterinary Internal Medicine 31 pp. 505-512 Wiley
Background:

The term meningoencephalocele (MEC) describes a herniation of cerebral tissue and meninges through a defect in the cranium, whereas a meningocele (MC) is a herniation of the meninges alone. Hypothesis/Objectives: To describe the clinical features, magnetic resonance imaging (MRI) characteristics, and outcomes of dogs with cranial MC and MEC. Animals: Twenty-two client-owned dogs diagnosed with cranial MC or MEC.

Methods:

Multicentric retrospective descriptive study. Clinical records of 13 institutions were reviewed. Signalment, clinical history, neurologic findings and MRI characteristics as well as treatment and outcome were recorded and evaluated.

Results:

Most affected dogs were presented at a young age (median, 6.5 months; range, 1 month ? 8 years). The most common presenting complaints were seizures and behavioral abnormalities. Intranasal MEC was more common than parietal MC. Magnetic resonance imaging identified meningeal enhancement of the protruded tissue in 77% of the cases. Porencephaly was seen in all cases with parietal MC. Cerebrospinal fluid (CSF) analysis identified mild abnormalities in 4 of 11 cases. Surgery was not performed in any affected dog. Seventeen patients were treated medically, and seizures were adequately controlled with anti-epileptic drugs in 10 dogs. Dogs with intranasal MEC and mild neurologic signs had a fair prognosis with medical treatment.

Conclusion and clinical importance:

Although uncommon, MC and MEC should be considered as a differential diagnosis in young dogs presenting with seizures or alterations in behavior. Medical treatment is a valid option with a fair prognosis when the neurologic signs are mild.

Gredal H, Thomsen B, Boza-Serrano A, Garosi L, Rusbridge C, Anthony D, Møller A, Finsen B, Deierborg T, Lambertsen K, Berendt M (2017) Interleukin-6 is increased in plasma and cerebrospinal fluid of community-dwelling domestic dogs with acute ischaemic stroke, Neuroreport 28 (3) pp. 134-140 Lippincott, Williams & Wilkins
Inflammatory cytokines are potential modulators of infarct progression in acute ischaemic stroke, and are therefore possible targets for future treatment strategies. Cytokine studies in animal models of surgically induced stroke may, however, be influenced by the fact that the surgical intervention itself contributes towards the cytokine response. Community-dwelling domestic dogs suffer from spontaneous ischaemic stroke, and therefore, offer the opportunity to study the cytokine response in a noninvasive set-up. The aims of this study were to investigate cytokine concentrations in plasma and cerebrospinal fluid (CSF) in dogs with acute ischaemic stroke and to search for correlations between infarct volume and cytokine concentrations. Blood and CSF were collected from dogs less than 72 h after a spontaneous ischaemic stroke. Infarct volumes were estimated on MRIs. Interleukin (IL)-2, IL-6, IL- 8, IL-10 and tumour necrosis factor in the plasma, CSF and brain homogenates were measured using a canine-specific multiplex immunoassay. IL-6 was significantly increased in plasma (P=0.04) and CSF (P=0.04) in stroke dogs compared with healthy controls. The concentrations of other cytokines, such as tumour necrosis factor and IL-2, were unchanged. Plasma IL-8 levels correlated significantly with infarct volume (Spearman?s r=0.8, P=0.013). The findings showed increased concentrations of IL-6 in the plasma and CSF of dogs with acute ischaemic stroke comparable to humans. We believe that dogs with spontaneous stroke offer a unique, noninvasive means of studying the inflammatory processes that accompany stroke while reducing confounds that are unavoidable in experimental models.
Swain L, Key G, Tauro A, Ahonen S, Wang P, Ackerley C, Minassian B, Rusbridge C (2017) Lafora disease in miniature Wirehaired Dachshunds., PLoS ONE 12 (8) e0182024. Public Library of Science
Lafora disease (LD) is an autosomal recessive late onset, progressive myoclonic epilepsy with a high prevalence in the miniature Wirehaired Dachshund. The disease is due to a mutation in the Epm2b gene which results in intracellular accumulation of abnormal glycogen (Lafora bodies). Recent breed-wide testing suggests that the carrier plus affected rate may be as high as 20%. A characteristic feature of the disease is spontaneous and reflex myoclonus; however clinical signs and disease progression are not well described. A survey was submitted to owners of MWHD which were homozygous for Epm2b mutation (breed club testing program) or had late onset reflex myoclonus and clinical diagnosis of LD. There were 27 dogs (11 male; 16 female) for analysis after young mutation-positive dogs that had yet to develop disease were excluded. Average age of onset of clinical signs was 6.94 years (3.5?12). The most common initial presenting sign was reflex and spontaneous myoclonus (77.8%). Other presenting signs included hypnic myoclonus (51.9%) and generalized seizures (40.7%). Less common presenting signs include focal seizures, ?jaw smacking?, ?fly catching?, ?panic attacks?, impaired vision, aggression and urinary incontinence. All these clinical signs may appear, and then increase in frequency and intensity over time. The myoclonus in particular becomes more severe and more refractory to treatment. Signs that developed later in the disease include dementia (51.9%), blindness (48.1%), aggression to people (25.9%) and dogs (33.3%), deafness (29.6%) and fecal (29.6%) and urinary (37.0%) incontinence as a result of loss of house training (disinhibited type behavior). Further prospective study is needed to further characterize the canine disease and to allow more specific therapeutic strategies and to tailor therapy as the disease progresses.
Nalborczyk Z, McFadyen A, Jovanovik J, Tauro A, Driver C, Fitzpatrick N, Knower S, Rusbridge C (2017) MRI characteristics for ?phantom? scratching in canine syringomyelia, BMC Veterinary Research 13 (1) BioMed Central

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.

Packer R, Berendt M, Bhatti S, Charalambous M, Cizinauskas S, De Risio L, Farquhar R, Hampel R, Hill M, Mandigers P, Pakozdy A, Preston S, Rusbridge C, Stein V, Taylor-Brown F, Tipold A, Volk H (2015) Inter-observer agreement of canine and feline paroxysmal event semiology and classification by veterinary neurology specialists and non-specialists, BMC Veterinary Research 11 (39) BioMed Central
Background:

Advances in mobile technology mean vets are now commonly presented with videos of paroxysmal
events by clients, but the consistency of the interpretation of these videos has not been investigated. The objective of
this study was to investigate the level of agreement between vets (both neurology specialists and non-specialists) on
the description and classification of videos depicting paroxysmal events, without knowing any results of diagnostic
workup. An online questionnaire study was conducted, where participants watched 100 videos of dogs and cats
exhibiting paroxysmal events and answered questions regarding: epileptic seizure presence (yes/no), seizure type,
consciousness status, and the presence of motor, autonomic and neurobehavioural signs. Agreement statistics
(percentage agreement and kappa) calculated for each variable, with prevalence indices calculated to aid their
interpretation.

Results:

Only a fair level of agreement (º = 0.40) was found for epileptic seizure presence. Overall agreement of
seizure type was moderate (º = 0.44), with primary generalised seizures showing the highest level of agreement
(º = 0.60), and focal the lowest (º =0.31). Fair agreement was found for consciousness status and the presence of
autonomic signs (º = 0.21?0.40), but poor agreement for neurobehavioral signs (º = 0.16). Agreement for motor
signs ranged from poor (º = d 0.20) to moderate (º = 0.41?0.60). Differences between specialists and non-specialists
were identified.

Conclusions:

The relatively low levels of agreement described here highlight the need for further discussions
between neurology experts regarding classifying and describing epileptic seizures, and additional training of
non-specialists to facilitate accurate diagnosis. There is a need for diagnostic tools (e.g. electroencephalogram)
able to differentiate between epileptic and non-epileptic paroxysms.

Knowler S, V/D Berg H, McFadyen A, La Ragione R, Rusbridge C (2016) Inheritance of Chiari-Like Malformation: Can a Mixed Breeding Reduce the Risk of Syringomyelia?, PLoS One 11 (3) ARTN e0151280 Public Library of Science (PLoS)
Canine Chiari-like malformation (CM) is a complex abnormality of the skull and craniocervical junction associated with miniaturization and brachycephaly which can result in the spinal cord disease syringomyelia (SM). This study investigated the inheritance of CM in a Griffon Bruxellois (GB) family and feasibility of crossbreeding a brachycephalic CM affected GB with a mesaticephalic normal Australian terrier and then backcrossing to produce individuals free of the malformation and regain GB breed characteristics. The study family cohort (n = 27) included five founder dogs from a previous baseline study of 155 GB which defined CM as a global malformation of the cranium and craniocervical junction with a shortened skull base and increased proximity of the cervical vertebrae to the skull. T1-weighted sagittal DICOM images of the brain and craniocervical junction were analysed for five significant traits (two angles, three lines) identified from the previous study and subsequent Qualitative Trait Loci analysis. Mean measurements for mixed breed, pure-breed and baseline study groups were compared. Results indicated that mixed breed traits posed less risk for CM and SM and were useful to distinguish the phenotype. Moreover on the MR images, the filial relationships displayed by the traits exhibited segregation and those presenting the greatest risk for CM appeared additive towards the severity of the condition. The external phenotypes revealed that by outcrossing breed types and with careful selection of appropriate conformation characteristics in the first generation, it is possible to regain the GB breed standard and reduce the degree of CM. The four GB affected with SM in the study all exhibited reduced caudal skull development compared to their relatives. The craniocervical traits may be useful for quantifying CM and assessing the possibility of SM thus assisting breeders with mate selection. However, such a system requires validation to ensure appropriateness for all breeds at risk.
Tauro A, Addicott D, Foale R, Bowman C, Hahn C, Long S, Massey J, Haley A, Knowler S, Day M, Kennedy L, Rusbridge C (2015) Clinical features of idiopathic inflammatory polymyopathy in the Hungarian Vizsla, BMC Veterinary Research 11 (97) BioMed Central
Background

A retrospective study of the clinicopathological features of presumed and confirmed cases of idiopathic inflammatory polymyopathy in the Hungarian Vizsla dog and guidelines for breeding.

Results

369 medical records were reviewed (1992?2013) and 77 Hungarian Vizslas were identified with a case history consistent with idiopathic inflammatory polymyopathy. Inclusion criteria were: group 1 (confirmed diagnosis); histopathology and clinical findings compatible with an inflammatory polymyopathy and group 2 (probable diagnosis); clinical findings compatible with a polymyopathy including dysphagia, sialorrhea, temporal muscle atrophy, elevated serum creatine kinase (CK) activity, and sufficient clinical history to suggest that other neuromuscular disorders could be ruled out. Some group 2 dogs had muscle biopsy, which suggested muscle disease but did not reveal an inflammatory process. The mean age of onset was 2.4 years; male dogs were slightly overrepresented. Common presenting signs were dysphagia, sialorrhea, masticatory muscle atrophy, and regurgitation. Common muscle histopathological findings included degenerative and regenerative changes, with multifocal mononuclear cell infiltration with lymphoplasmacytic myositis of variable severity. A positive response to immunosuppressive treatment supported an immune-mediated aetiology. The mean age at death and survival time were 6.4 and 3.9 years, respectively. Recurrence of clinical signs and aspiration pneumonia were common reasons for euthanasia.

Conclusions

Diagnosis of Vizsla idiopathic inflammatory polymyopathy can be challenging due to lack of specific tests, however the presence of dysphagia, regurgitation and masticatory muscle atrophy in this breed with negative serological tests for masticatory muscle myositis and myasthenia gravis, along with muscle biopsies suggesting an inflammatory process, support the diagnosis. However, there is an urgent need for a more specific diagnostic test. The average of inbreeding coefficient (CoI) of 16.3% suggests an increased expression of a Dog Leukocyte Antigen Class II haplotype, leading to an increased disease risk. The prognosis remains guarded, as treatment can only manage the disease. Recurrence of clinical signs and perceived poor quality of life are the most common reasons for humane euthanasia.

Lemay P, Knowler S, Bouasker S, Nédélec Y, Platt S, Freeman C, Child G, Barreiro L, Rouleau G, Rusbridge C, Kibar Z (2014) Quantitative Trait Loci (QTL) Study Identifies Novel Genomic Regions Associated to Chiari-Like Malformation in Griffon Bruxellois Dogs, PLoS ONE 9 (4) e89816 Public Library of Science
Chiari-like malformation (CM) is a developmental abnormality of the craniocervical junction that is common in the Griffon Bruxellois (GB) breed with an estimated prevalence of 65%. This disease is characterized by overcrowding of the neural parenchyma at the craniocervical junction and disturbance of cerebrospinal fluid (CSF) flow. The most common clinical sign is pain either as a direct consequence of CM or neuropathic pain as a consequence of secondary syringomyelia. The etiology of CM remains unknown but genetic factors play an important role. To investigate the genetic complexity of the disease, a quantitative trait locus (QTL) approach was adopted. A total of 14 quantitative skull and atlas measurements were taken and were tested for association to CM. Six traits were found to be associated to CM and were subjected to a whole-genome association study using the Illumina canine high density bead chip in 74 GB dogs (50 affected and 24 controls). Linear and mixed regression analyses identified associated single nucleotide polymorphisms (SNPs) on 5 Canis Familiaris Autosomes (CFAs): CFA2, CFA9, CFA12, CFA14 and CFA24. A reconstructed haplotype of 0.53 Mb on CFA2 strongly associated to the height of the cranial fossa (diameter F) and an haplotype of 2.5 Mb on CFA14 associated to both the height of the rostral part of the caudal cranial fossa (AE) and the height of the brain (FG) were significantly associated to CM after 10 000 permutations strengthening their candidacy for this disease (P
=
0.0421, P
=
0.0094 respectively). The CFA2 QTL harbours the Sall-1 gene which is an excellent candidate since its orthologue in humans is mutated in Townes-Brocks syndrome which has previously been associated to Chiari malformation I. Our study demonstrates the implication of multiple traits in the etiology of CM and has successfully identified two new QTL associated to CM and a potential candidate gene.
Kiviranta A, Rusbridge C, Laitinen-Vapaavuori O, Hielm-Bjorkman A, Lappalainen A, Knowler S, Jokinen T (2017) Syringomyelia and Craniocervical Junction Abnormalities in Chihuahuas, J Vet Intern Med 31 (6) pp. 1771-1781 Wiley
Background:

Chiari-like malformation (CM) and syringomyelia (SM) are widely reported in Cavalier King Charles Spaniels
and Griffon Bruxellois dogs. Increasing evidence indicates that CM and SM also occur in other small and toy breed
dogs, such as Chihuahuas.

Objectives:

To describe the presence of SM and craniocervical junction (CCJ) abnormalities in Chihuahuas and to evaluate
the possible association of CCJ abnormalities with SM. To describe CM/SM-related clinical signs and neurologic deficits
and to investigate the association of CM/SM-related clinical signs with signalment, SM, or CCJ abnormalities.
Animals: Fifty-three client-owned Chihuahuas.

Methods:

Prospective study. Questionnaire analyses and physical and neurologic examinations were obtained before magnetic
resonance and computed tomography imaging. Images were evaluated for the presence of SM, CM, and atlantooccipital
overlapping. Additionally, medullary kinking, dorsal spinal cord compression, and their sum indices were calculated.
Results: Scratching was the most common CM/SM-related clinical sign and decreased postural reaction the most common
neurologic deficit in 73 and 87% of dogs, respectively. Chiari-like malformation and SM were present in 100 and 38% of
dogs, respectively. Syringomyelia was associated with the presence of CM/SM-related clinical signs (P = 0.034), and medullary
kinking and sum indices were higher in dogs with clinical signs (P = 0.016 and P = 0.007, respectively).

Conclusions and Clinical Importance:

Syringomyelia and CCJ abnormalities are prevalent in Chihuahuas. Syringomyelia
was an important factor for the presence of CM/SM-related clinical signs, but many dogs suffered from similar clinical signs
without being affected by SM, highlighting the clinical importance of CCJ abnormalities in Chihuahuas.

Knowler S, McFadyen A, Freeman C, Kent M, Platt S, Kibar Z, Rusbridge C (2014) Quantitative Analysis of Chiari-Like Malformation and Syringomyelia in the Griffon Bruxellois Dog, PLoS ONE 9 (2) e88120 Public Library of Science
This study aimed to develop a system of quantitative analysis of canine Chiari-like malformation and syringomyelia on
variable quality MRI. We made a series of measurements from magnetic resonance DICOM images from Griffon Bruxellois
dogs with and without Chiari-like malformation and syringomyelia and identified several significant variables. We found that
in the Griffon Bruxellois dog, Chiari-like malformation is characterized by an apparent shortening of the entire cranial base
and possibly by increased proximity of the atlas to the occiput. As a compensatory change, there appears to be an increased
height of the rostral cranial cavity with lengthening of the dorsal cranial vault and considerable reorganization of the brain
parenchyma including ventral deviation of the olfactory bulbs and rostral invagination of the cerebellum under the occipital
lobes.
Rusbridge C (2014) Chiari?like malformation and syringomyelia, European Journal Companion Animal Practice 23 (3) pp. 70-89 Federation of European Companion Animal Veterinary Associations
Syringomyelia is a condition characterised by fluid filled cavities (syrinxes or syringes) within
the central spinal cord and the resulting damage produces clinical signs of pain and neurological
deficits. Since the increase in availability of magnetic resonance imaging (MRI), syringomyelia
is an increasingly common diagnosis in veterinary medicine [1, 2] The most common cause of
syringomyelia in the dog is Chiari-like malformation (Fig 1), a condition analogous to Chiari Type I
and 0 malformation in humans [3, 4].
Cockburn A, Smith M, Rusbridge Clare, Fowler C, Paul E, Murrell J, Blackwell E, Casey R, Whay H, Mendl M (2017) Evidence of negative affective state in Cavalier King Charles Spaniels with syringomyelia, Applied Animal Behaviour Science 201 pp. 77-84 Elsevier
Syringomyelia is a common and chronic neurological disorder affecting Cavalier King Charles Spaniels. The condition is putatively painful, but evaluating the affective component of chronic pain in non-human animals is challenging. Here we employed two methods designed to assess animal affect ? the judgement bias and reward loss sensitivity tests ? to investigate whether Cavalier King Charles Spaniels with syringomyelia (exhibiting a fluid filled cavity (syrinx) in the spinal cord of e2mm diameter) were in a more negative affective state than those without the condition. Dogs with syringomyelia did not differ in age from those without the condition, but owners reported that they scratched more (P
Rusbridge C, Salguero Bodes F, David M, Faller K, Bras J, Guerreiro R, Richard-Loendt A, Grainger D, Head E, Brandner S, Summers B, Hardy J, Tayebi M (2018) An aged canid with behavioural deficits exhibits blood and cerebrospinal fluid amyloid beta oligomers, Frontiers in Aging Neuroscience 10 7 pp. 1-8 Frontiers Media
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 behaviour and memory the severity of cognitive dysfunction parallels the progressive build up and location of A² in the brain. The main aim of this work was to study the biological behaviour of soluble oligomers isolated from an aged dog with cognitive dysfunction through investigating their interaction with a human cell line and synthetic A² peptides. We report that soluble oligomers were specifically detected in the dog?s blood and cerebrospinal fluid via anti-oligomer- and anti-A² specific binders.
Importantly, our results reveal the potent neurotoxic effects of the dog?s cerebrospinal fluid on cell viability and the seeding efficiency of the cerebrospinal fluid-borne soluble oligomers on the thermodynamic activity and the aggregation kinetics of synthetic human A². The value of further characterising the naturally occurring Alzheimer-like neuropathology in dogs using genetic and molecular tools is discussed.
Cirovic Srdjan, Lloyd R, Jovanovik J, Volk H, Rusbridge Clare (2018) Computer simulation of syringomyelia in dogs, BMC Veterinary Research 14 (82) BioMed Central
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.

Ancot F, Lemay P, Knowler S, Kennedy K, Griffiths S, Cherubini G, Sykes J, Mandigers P, Rouleau G, Rusbridge C, Kibar Z (2018) A genome-wide association study identifies
candidate loci associated to syringomyelia
secondary to Chiari-like malformation in
Cavalier King Charles Spaniels,
BMC Genetics 19 (16) BioMed Central
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.

Gandolfi B, Alhaddad H, Abdi M, Bach L, Creighton E, Davis B, Decker J, Dodman N, Grahn J, Grahn R, Haase B, Haggstrom J, Hamilton M, Helps C, Kurushima J, Lohi H, Longeri M, Malik R, Meurs K, Montague M, Mullikin J, Murphy W, Nilson S, Pedersen N, Peterson C, Rusbridge C, Saif R, Shelton D, Warren W, Wasim M, Lyons L (2018) Applications and efficiencies of the first cat 63K DNA array, Scientific Reports 8 (1) 7024 pp. 1-15 Nature Publishing Group
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 Infnium 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 efciency 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 confrmed 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 diferent modes of inheritance, selection and population sizes. The
efcient 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.
Batle P, Rusbridge C, Nuttall T, Heath S, Marioni-Henry K (2018) Feline hyperaesthesia syndrome with self-trauma to the tail: retrospective study of seven cases and proposal for integrated multidisciplinary diagnostic approach, Journal of Feline Medicine and Surgery SAGE Publications
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).
Watson F, Rusbridge Clare, Packer RMA, Casey RA, Heath S, Volk HA (2018) A review of treatment options for behavioural manifestations of clinical anxiety as a comorbidity in dogs with idiopathic epilepsy, The Veterinary Journal 238 pp. 1-9 Elsevier
Psychiatric comorbidities affect a large percentage of people with epilepsy and have a detrimental impact on their quality of life. Recently, behavioural comorbidities, with similar characteristics to human psychiatric diseases, have been identified in dogs with idiopathic epilepsy. In particular, behaviours motivated by the fear?anxiety emotional system have been found to be associated with the occurrence of idiopathic epilepsy in both dogs receiving anti-epileptic drugs, and drug-naïve dogs. There has been little research into the relationship between epilepsy and behavioural signs, and even less into potential treatment protocols. The following article will review available literature from human medicine to describe the current state of knowledge about the bi-directional relationship between anxiety and epilepsy, draw parallels from reported anxiogenic and anxiolytic properties of anti-epileptic drugs and attempt to provide pharmaceutical and behavioural guidance for veterinary patients with epilepsy and comorbid anxiety.
Brocal J, De Decker S, Jose-Lopez R, Manzanilla EG, Penderis J, Stalin C, Bertram S, Schoenebeck JJ, Rusbridge Clare, Fitzpatrick Noel, Gutierrez?Quintana R (2018) C7 vertebra homeotic transformation in domestic dogs - are Pug dogs breaking mammalian evolutionary constraints?, Journal of Anatomy 233 (2) pp. 255-265 Wiley
The number of cervical vertebrae in mammals is almost constant at seven, regardless of their neck length, implying that there is selection against variation in this number. Homebox (Hox) genes are involved in this evolutionary mammalian conservation, and homeotic transformation of cervical into thoracic vertebrae (cervical ribs) is a common phenotypic abnormality when Hox gene expression is altered. This relatively benign phenotypic change can be associated with fatal traits in humans. Mutations in genes upstream of Hox, inbreeding and stressors during organogenesis can also cause cervical ribs. The aim of this study was to describe the prevalence of cervical ribs in a large group of domestic dogs of different breeds, and explore a possible relation with other congenital vertebral malformations (CVMs) in the breed with the highest prevalence of cervical ribs. By phenotyping we hoped to give clues as to the underlying genetic causes. Twenty computed tomography studies from at least two breeds belonging to each of the nine groups recognized by the Federation Cynologique Internationale, including all the brachycephalic ?screw?tailed? breeds that are known to be overrepresented for CVMs, were reviewed. The Pug dog was more affected by cervical ribs than any other breed (46%; P?0.001), and was selected for further analysis. No association was found between the presence of cervical ribs and vertebral body formation defect, bifid spinous process, caudal articular process hypoplasia/aplasia and an abnormal sacrum, which may infer they have a different aetiopathogenesis. However, Pug dogs with cervical ribs were more likely to have a transitional thoraco?lumbar vertebra (P?=?0.041) and a pre?sacral vertebral count of 26 (P?0.001). Higher C7/T1 dorsal spinous processes ratios were associated with the presence of cervical ribs (P?0.001), supporting this is a true homeotic transformation. Relaxation of the stabilizing selection has likely occurred, and the Pug dog appears to be a good naturally occurring model to further investigate the aetiology of cervical ribs, other congenital vertebral anomalies and numerical alterations.
Spocter Muhammad A, Uddin Ashraf, Ng Johnny C, Wong Edmund, Wang Victoria X, Tang Cheuk, Wicinski Bridget, Haas Jordan, Bitterman Kathleen, Raghanti Mary Ann, Dunn Rachel, Hof Patrick R, Sherwood Chet C, Jovanovik Jelena, Rusbridge Clare, Manger Paul R (2018) Scaling of the corpus callosum in wild and domestic canids: Insights into the domesticated brain., JOURNAL OF COMPARATIVE NEUROLOGY 526 (15) pp. 2341-2359 WILEY-LISS
All domesticated mammals exhibit marked reductions in overall brain size, however, it is unknown whether the corpus callosum, 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 mid?sagittal cross?sectional areas of the corpus callosum in 35 carnivore species, including eight wild canids and 13 domestic dogs. We segmented rostro?caudal regions of interest for the corpus callosum and evaluated correlations with brain mass. The results of this study indicate that under the influence of domestication in canids, the corpus callosum 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 corpus callosum relative to overall brain size, however fibers passing through the rostrum, putatively connecting prefrontal cortex, are less constrained and therefore may contribute more towards 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.
Knowler Susan P, Galea Gabriel L, Rusbridge Clare (2018) Morphogenesis of canine Chiari malformation and secondary syringomyelia: Disorders of cerebrospinal fluid circulation, Frontiers in Veterinary Science 5 171 Frontiers Media
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.
Trace C., Rusbridge C. (2018) Combination of a Xerte Bootstrap and Survey to teach Neurological Examination, Proceedings of the VSC Veterinary Education Symposium (VetEd) 2018 Veterinary Schools Council (VSC)
A resource was created for a third-year Neurology module using the Xerte Bootstrap template. Students were given 3 hours to work through cases and log answers in an online survey, then 1 hour for a wrap-up session where group answers were discussed then answers revealed. This format proved overwhelmingly positive for students.

Background: Chiari-like malformation (CM) is a complex malformation of the skull and cranial cervical vertebrae potentially resulting in pain and secondary syringomyelia (SM). CM associated pain can be challenging to diagnose [35]. We propose a machine learning approach to characterize morphological changes in dogs that may/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: Using a novel machine learning approach to understand neuromorphological change and to identify image-based biomarkers in dogs with CM associated pain (CM-P) and symptomatic SM (SM-S), with the aim of deepening the understanding on these disorders.
Animals: 32 client owned Cavalier King Charles Spaniels (CKCS) (11 controls, 10 CM-P, 11 SM-S)

Methods: Retrospective study using T2W midsagittal DICOM anonymized images which were mapped to a images of a 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 (ROC) 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 biomarkers collectively.

Conclusions and clinical importance:
Machine learning techniques can assist CM/SM diagnosis and understand abnormal morphology location with the potential to be applied to a variety of breeds and conformational diseases.