Research into syringomyelia


 Projects in US and UK, compiled by Carol Fowler:
 
COLLECTION AND ARCHIVING OF CAVALIER KING CHARLES SPANIEL DNA, TO IDENTIFY THE MODE OF INHERITANCE AND GENES RESPONSIBLE FOR SYRINGOMYELIA, MVD AND EPILEPSY
CLARE RUSBRIDGE  BVMS, Dip ECVN, MRCVS, European and RCVS Specialist in Veterinary Neurology, and PENNY KNOWLER  BSc
The Stone Lion Veterinary Centre, Wimbledon, London, UK
Clare Rusbridge first described the disease when a resident at the Royal College of Veterinary Surgeons in 1997.  She later established that the disease was inherited.  Over the past 8 years she has continued to research this disease, focusing on the genetics, pathogenesis and treatment, while undertaking a PhD on Occipital Hypoplasia / Syringomyelia, based at Utrecht University. She is currently collaborating with Dr Guy Rouleau, MD PhD FRCP, at the Centre for the Study of Brain Diseases, CHUM Research Centre, Montreal, and Dr Berge Minassian, MD CM FRCP,  Centre for Applied Genomics, at the Hospital for Sick Kids, Toronto, Canada.
Their research aims to include the identification and characterisation of genetic factors predisposing to Chiari 1 malformation, to increase the understanding of the pathophysiology of SM, for better diagnosis, clinical management and ultimate prevention.  The initial stage of this undertaking is nearing completion with the collection and archiving of Cavalier King Charles Spaniel DNA.  This has been achieved by the support of the Cavalier Club UK, the UK DNA archive, Boehringer Ingelheim Limited, CKCS Club USA Health Foundation, veterinarians, pet owners and breeders worldwide. You can find out about contributing DNA for this important project here.
 
Publications to date:
Syringomyelia in Cavalier King Charles Spaniels. RUSBRIDGE, MACSWEENY, DAVIES, et al.  J Am Anim Hosp Assoc, 2000 36: 34-41
Dorsal dens angulation and a Chiari malformation in a Cavalier King Charles Spaniel.  BYNEVELT, RUSBRIDGE, BRITTON.  Veterinary Radiology and Ultrasound, 2000, 41
Hereditary aspects of occipital bone hypoplasia and syringomyelia (Chiari type 1 malformation) in Cavalier King Charles Spaniels.  RUSBRIDGE, KNOWLER. The Veterinary Record, July 26 2003
Syringomyelia  RUSBRIDGE.  UK Vet Vol 8 No 8 November 2003
Inheritance of occipital bone hypoplasia (Chiari 1 malformation) in Cavalier King Charles Spaniels. RUSBRIDGE, KNOWLER.  Journal of Veterinary Internal Medicine 2004, 18
Neurological Diseases in Cavalier King Charles Spaniels.  RUSBRIDGE. Journal of Small Animal Practice 2005, 46
Inherited occipital hypoplasia/syringomyelia in the Cavalier King Charles Spaniel - experiences in setting up a worldwide DNA collection.  RUSBRIDGE, KNOWLER, ROULEAU, MINASSIAN, ROTHUIZEN.  Awaiting publication in Journal of Heredity, 2005
 
NEUROLOGICAL SIGNS AND RESULTS OF MAGNETIC RESONANCE IMAGING IN 40 CAVALIER KING CHARLES SPANIELS WITH CHIARI TYPE 1-LIKE MALFORMATIONS
D. LU, C LAMB, D PFEIFFER, M TARGETT
The Royal Veterinary College, Hertfordshire, UK
Veterinary Record, August 30, 2003
The study found that the dogs had a wide variety of neurological signs, but there was no apparent correlation between the neurological signs and the severity of  cerebellar herniation, syringohydromyelia, or hydrocephalus.
 
CAVALIER KING CHARLES SPANIEL HEALTH SURVEY
DR LARRY GLICKMAN
Purdue University School of Veterinary Medicine, West Lafayette, Indiana, USA
The study aims to identify health trends in the breed along with diseases and disorders prevalence.  To retain geneticist(s) and a canine genetics counsellor to address each concern carefully, reviewing them with each generation.  Develop a university based clearing house for MRI, Cardiac and DNA research.
 
THE STUDY OF CAUDAL OCCIPITAL MALFORMATION SYNDROME (COMS) IN CAVALIER KING CHARLES SPANIELS
CARLY ABRAMSON, DVM, Assoc Prof. and PHIL MARCH, DVM
The Ohio State University School of Veterinary Medicine, USA
Caudal Occipital Malformation Syndrome (COMS), similar to Chiari malformation in humans, is a recognised problem affecting the Cavalier King Charles Spaniel breed, which can lead to the development of neurological disease.  Currently, treatment recommendations are based on the presence of progressive neurological deterioration.  There are no objective parameters to evaluate affected patients which are at risk for developing neurological disease prior to clinical deterioration.  Researchers hypothesise that Magnetic Resonance Imaging (MRI) and ultrasound parameters can be used to predict dogs at risk, and objectively evaluate efficacy of therapy for this disorder.
The objective of this study is to evaluate a family of CKCS that includes clinically affected and clinically normal dogs.  Measurements of ventricle size, foramen magnum size, and spinal cord dilation, as well as cerebrospinal fluid (CSF) flow velocity studies at the foramen magnum, will be evaluated on MRI.  Basilar artery resistive index obtained with ultrasound will be assessed.  The dogs will be monitored over 2 years to determine the ability of these objective parameters to predict clinical disease progression.  For those patients receiving medical or surgical treatment of COMS, each diagnostic test will be applied post-treatment to evaluate their ability to monitor success of treatment.
 
THE EFFECT OF CHIARI TYPE 1 MALFORMATIONS ON CSF FLOW IN CAVALIER KING CHARLES SPANIELS
DR NATASHA OLBY and DR SOPHIA CERDA-GONZALEZ
North Carolina State University Veterinary School, USA, May 2005
This study aims to compare CSF flow patterns and velocity at the level of the foramen magnum between three groups of Cavalier King Charles Spaniels:  normal CKCS, symptomatic CKCS, and asymptomatic CKCS with Chiari malformations.  Researchers will also begin to establish the incidence of asymptomatic Chiari malformations in a group of CKCS, as well as investigate the genetics of this disorder.
The pattern and velocity of CSF flow can be measured using a specialised, non-invasive MRI technique called PVC MRI.  The researchers' aims are to determine the site of peak flow and turbulence (which will aid in determining the most appropriate surgical approach to treating the disease), and to determine what CSF flow velocity is the threshold for developing clinical signs.  The study will also allow the screening of potential breeding dogs for the presence of the disease, and will allow researchers to estimate the incidence of asymptomatic disease in CKCS in North Carolina and surrounding regions.
 
PROPOSED SEQUENTIAL MRI STUDY OF CKCS LITTERS
DR CURTIS DEWEY
Long Island Veterinary Specialists, New York, USA
Dr Dewey plans to start a project of sequentially MRI scanning litters of CKCS pups, in order to identify the prevalence of the malformation and the progression of the disorder.  He plans to focus on early surgical intervention in symptomatic puppies, to determine whether or not such intervention is more likely to lead to disease resolution, than operating at adulthood.  Dr Dewey's emphasis is on finding the most effective treatment options for dogs affected with COMS.
 
THE USE OF ULTRASONOGRAPHY TO DIAGNOSE ‘CAUDAL OCCIPITAL MALFORMATION SYNDROME’ IN DOGS – A PROSPECTIVE STUDY IN 12 DOGS
B LEVITIN, J MACDONNELL, A TIDWELL
 
Tufts University School of Veterinary Medicine, North Grafton, MA, US.
 
The goal of this study was to determine the utility of cervical spinal cord ultrasonography (U/S) to complement magnetic resonance imaging (MRI) for the diagnosis of COMS.  The procedure is described and a comparison made between U/S and MRI findings in dogs with and without COMS.
 
The study group consisted of 9 dogs that were diagnosed with COMS by MRI and 3 that were not.  All dogs had cervical U/S performed.  Sonographic images were obtained by a certified radiologist with a 5-8 MHz transducer.  No anesthesia was required.  A dorsal midline acoustic window through the cisterna magnum and a dorsolateral oblique acoustic window through the atlanto-axial intervertebral foramen were used.  Specific attention was made to the presence of cerebellar coning, ‘medullary kink’, syringohydromyelia, and ventricular enlargement.  Findings were that 4/9 study dogs had U/S diagnosis of COMS, 3/9 study dogs were suspicious of COMS, and 2/9 study dogs were normal.  All control dogs were normal.
 
This preliminary study indicates that cervical spinal cord ultrasound can be useful as a diagnostic aid for COMS.  It cannot rule out a diagnosis of COMS, however no false positives were found.  To investigate the sensitivity and specificity of this imaging modality blinded U/S examination of large numbers of dogs after MRI evaluation is planned.
 
DOES HEAD POSITION AFFECT THE APPARENT SEVERITY OF THE MALFORMATIONS ASSOCIATED WITH SYRINGOMYELIA IN THE CAVALIER KING CHARLES SPANIEL?
DR CLARE RUBRIDGE and DR NICK JEFFERY, funded by the UK CKCS Club
 
Early MRI screening has been proposed as a means to reduce clinical syringomyelia in the breed.  However, precise criteria for quantifying the abnormality have yet to be determined.  It is not known, for instance, whether the position of the dog’s head in the MRI receiving coil could make an abnormality more apparent.  In this study researchers propose to investigate whether position influences the MRI scan results.  
 
This information is not only important in establishing an accurate pre-breeding test but is also important for the current genetic research.  At present the genome scan is in process.  The accuracy of the scan is dependent on the accuracy of the phenotypic information, ie, knowledge of the severity of the malformation.  It is proposed to use 20-25 CKCS (an equal number of males and females) that are presented for routine pre-breeding MRI screening, with a view to establishing the presence or absence of occipital malformation/syringomyelia.  MRI images of the brain and upper cervical spine are obtained under a general anaesthetic.  After the routine images are obtained the position of the dog’s head is changed from extended to slightly flexed position and the sagittal images repeated.
 
 
COEXISTENCE OF OCCIPITAL DYSPLASIA AND OCCIPITAL HYPOPLASIA/SYRINGOMYELIA IN THE CAVALIER KING CHARLES SPANIEL
CLARE RUSBRIDGE,  PENNY KNOWLER  (Journal of Small Animal Practice, Oct 2006)
 
This study focussed on two CKCS which exhibited occipital hypoplasia and occipital dysplasia.  Occipital hypoplasia (Chiari malformation) 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, which is common in dogs with a rounded head shape, there is a failure of complete ossification of the supraoccipital bone.  Occipital dysplasia appears not to cause a functional problem because the overall shape and size of the caudal fossa are unchanged.  When the two conditions occur together, it is possible that syringomyelia may develop more slowly, resulting in the late presentation of signs.  It is possible that the membrane covering the supraoccipital defect allows for some expansion and less severe obstruction of the CSF movement through the foramen magnum.  In other words, dogs with occipital hypoplasia and occipital dysplasia may have a milder phenotype than those with occipital hypoplasia alone.  
 
This has implications for breeding as if the signs of onset of SM have been delayed by occipital dysplasia, then a dog may be erroneously thought to have a milder phenotype and used for breeding purposes.  
 
Whilst occipital hypoplasia can be easily seen from MRI images, occipital dysplasia cannot.  It is possible to detect dysplasia by radiographing the foramen magnum in a particular way, i.e. dorsal recumbency, the nose flexed at 25 to 40 degrees, and the x-ray beam centred on the frontal sinus.
 
 
SYRINGOMYELIA: CURRENT CONCEPTS IN PATHOGENESIS, DIAGNOSIS, AND TREATMENT
CLARE RUSBRIDGE, DAN GREITZ, AND BERMANS J. ISKANDER (Journal of Veterinary Internal Medicine 2006;20:469-479)
 
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 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.
 
 
2006 NORTH CAROLINA STATE UNIVERSITY REPORT ON MORPHOLOGY OF THE CAUSAL FOSSA IN CKCS
SONYA CERDA-GONZALEZ, NATASHA J OLBY, ET AL.
 
Chiari-like malformations and syringohydromyelia (SHM) make up a disease complex recognised in CKCS with a world-wide distribution, complex mode of inheritance and serious health implications.  The aim of the study was to evaluate the caudal fossa morphology in a group of 59 normal and affected CKCS, aged 1-5 years.  There were 11 clinically affected and 48 unaffected dogs.
 
The study recognised that there were several anatomical abnormalities (e.g. occipital dysplasia, cerebellar indentation, cerebellar herniation, medullary kinking) and sets out to discover the relationship between specific anatomical components and clinically evident disease.  
 
MRI Findings:
•    51 dogs were classified as morphologically abnormal (86%)
•    22 dogs had SHM (37%)
•    13 with SHM had no clinical signs
•    2 with clinical signs did not have SHM
•    50 had mild to marked cerebellar herniation and occipital dysplasia
•    39 had medullary kinking
•    55 had cerebellar crowding and indentation
•    12 had a dorsal compressive legion at the first and second cervical vertebral junction
 
Clinically affected dogs were more likely to have SHM than unaffected.
The ratio of caudal fossa volume to the total brain volume was significantly smaller in affected dogs.
The presence of SHM was not associated with the relative size of the caudal fossa.
No single abnormality was predictive of SHM or clinical status.
 
Follow up of the dogs over the next three years will establish whether these abnormalities predict future development of clinical signs.
 
NB  It is unclear whether this study’s use of the term ‘ occipital dysplasia’ is what Clare Rusbridge refers to as ‘occipital hypoplasia’. Occipital dysplasia is described in the Rusbridge/ Knowler article above.
 
 
2006 NORTH CAROLINA STATE UNIVERSITY REPORT ON CHARACTERISTICS OF CEREBROSPINAL FLUID FLOW IN CKCS
SONYA CERDA-GONZALEZ, NATASHA OLBY, ET AL
 
Changes of CSF flow are thought to cause Syringohydromyelia (SHM) associated with Chiari-like malformations.  Anatomical changes in the caudal fossa restrict CSF passage and result in high velocity jets and turbulence, causing syrinx formation.  Phase Velocity Cine MRI (PVC MRI) was used to evaluate CSF flow in a group of 59 affected and unaffected CKCS.  The affect of head position on CSF flow was assessed.  Flow characteristics were correlated with clinical status and morphological abnormalities.
 
The study found that CSF flow patterns and velocities were affected by head position.  In a normal standing position CSF flow velocity was increased in the dorsal subarachnoid space (SAS).  CSF flow was obvious within syrinxes, and in some cases peak velocity was highest in the syrinx.  Turbulent flow was mainly present in dogs with SHM at the level of the foramen magnum, cervical spinal cord, and could also be found within syrinxes.  CSF flow velocity may be higher within the dorsal SAS of affected dogs, although additional studies are needed.  Data will be reanalysed in the light of a longitudinal study of the long term clinical outcome of the dogs studied.
 
NB Both North Carolina Reports use the term Syringohydromyelia (SHM) instead of the more commonly used term Syringomyelia (SM).
 
 
 (To the best of my knowledge, the above information is accurate and correct, at the time of writing.
Carol Fowler, July 2006)

 
OTHER RESEARCH:
 
Sweden:
 
Undergraduate thesis, download (in Swedish, with images) available here:
http://ex-epsilon.slu.se/archive/00000866/
 
BAKRE SKALLGROPENS FORM HOS HUND: EN STUDIE AV OCCIPITAL HYPOPLASI HOS HUND
Spångberg, Camilla (2006) Bakre skallgropens form hos hund. Dept. of Small Animal Clinical Sciences, SLU. Examensarbete (Sveriges lantbruksuniversitet, Fakulteten för veterinärmedicin och husdjursvetenskap, Veterinärprogrammet) vol. 2006:51.
 
Abstract:
Chiari type I malformation is a condition in humans characterized by a small posterior cranial fossa, downward herniation of the cerebellar tonsils, foramen magnum overcrowding and disturbances of cerebrospinal fluid dynamics. Syringohydromyelia is often seen in patients with Chiari type I malformation. Syringohydromyelia is characterized by fluid-filled cavities in the spinal cord. This causes damage to the nervous tissue in the spinal cord. In recent years, a condition similar to Chiari type I malformation has been recognized in dogs. It has mostly been seen in Cavalier King Charles spaniels (CKCS). The condition seen in dogs is usually called occipital bone hypoplasia.
The aim of the study was to examine whether there is a difference in the shape of the caudal fossa between CKCS, small bred dogs with a similar head shape and dogs with a normal head shape and if occipital bone hypoplasia is related to a head shape with a steep back of the head. Other aims of the study were to examine the crowding of nervous tissue in the foramen magnum in each breed group, the extent of syringohydromyelia and to what extent the malformation had caused neurological signs.
Skulls from dogs on autopsy were divided in halves and the position of the cerebellum compared to the level of the foramen magnum was studied. The degree of crowding of nervous tissue in the foramen magnum was determined. Based on this the shape of the caudal fossa was classified as normal, possible occipital bone hypoplasia or occipital bone hypoplasia. The cervical spinal cord was extracted and examined for syringohydromyelia. To determine whether the malformation had caused any neurological signs, the medical records of the patients with occipital bone hypoplasia or possible occipital bone hypoplasia were studied. In cases where the medical records not include such information, the owners of the dogs were contacted and asked if they had noted any neurological signs in their dog.
This study showed that there is a difference in the shape of the caudal fossa between dogs with a normal head shape and small bred dogs with a steep back of the head. This indicates that occipital bone hypoplasia is related to a head shape where the back of the head is steep and that the malformation is common in these breeds. The study also showed that occipital bone hypoplasia not inevitably causes syringohydromyelia. Only one of the dogs with occipital bone hypoplasia or possible bone hypoplasia had had neurological signs that with certainty were related to the malformation. This result gives further support to previous studies that have stated that occipital bone hypoplasia occurs asymptomatic.
Note: this study was a student project and included a small number of dogs