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The Cavalier King Charles Spaniel Club has for some time been dedicated to research and awareness of Mitral Valve Disease, but 2004 is set to see an even greater concentration of activity.

In 2002 the Lub Dub Fund was set up to raise money for research into MVD. The magnificent efforts of Breed Clubs, individual Members and groups has already raised £24,895.00 for this Fund. They must all take a great deal of the credit and the effects of this will be witnessed far into the future of the breed.

Richard Han, The Club's sponsored Post Graduate student, has started his heart research project into Mitral Valve Endocardiosis at Edinburgh University. It is hoped that Richard's dedication to the topic will bring new knowledge and enlightenment about the condition.

Following an approach made by The Club, The Kennel Club Charitable Trust has very generously agreed to support the research at Edinburgh University. The Trust has guaranteed the sum of £22,950 and this further funding will enable the project to be extended to a three year PHD course. This is obviously a splendid boost for the Club's Fund Raising and its morale.

By using powerful molecular biology tools, the researchers will be attempting to discover what is happening to the valves at the cellular level. It is suspected that the reason dogs develop MVD is because a cell type, known as a valvular intestitial cell, within the valve structure begins to malfunction and fails to produce normal structural components. These components are crucial to maintaining the valve structural rigidity, its shape and function, and so prevent it from leaking.

As the CKCS Club has now reached its fund raising goal, with more success than it dared dream of, the Club officially closed the Fund on the 28th March this year.

In addition to all this current fundraising activity, The Cavalier Club has conducted a Heart Research Scheme since 1990, involving certification for dogs volunteered for testing. The results of these heart tests are then held on a database. A cardiologist has also attended our Championship Shows and several of our Open Shows each year to conduct more tests. The Club has also held Seminars, and has the active support of The Kennel Club, The Animal Health Trust and Edinburgh University.

New in 2003 was an innovative project, The Healthy Heart Partnership was established with Boehringer Ingelheim. The Club plans to hold a Health Clinic in Essex on 25th April and in the Bristol area in October. A third Clinic will be held in the Cheshire area, later in the year and the date will be announced shortly. These clinics will involve heart and eye testing, and offer a chance for Club members and non-Club members to learn about the conditions and ensure they are providing the best possible care for their dogs.

Several new heart based events took place throughout the year and 2004 will see an expansion of these activities.

As an extension of the Healthy Hearts Partnership, with partner funding from Boehringer Ingelheim. the Club is cooperating in a blood sampling project. The objective of this project is the development of a gene test for both MVD and Syringomyelia. An official Research Fund has been opened and several people have already expressed interest in helping. This will attack the heart problem on another front, and will also be a vital contribution to the research into Syringomyelia.

ICHTHYOSIS KERATOCONJUNCTIVITIS SICCA (Dry eye/curly coat)

There have been 21 separate cases of the condition submitted to the AHT since the research started. This does not take into account the many undiagnosed cases that went unreported due to lack of knowledge. It is now believed that there were in the order of some 39 or more cases that the Michigan State University and the University of Tennessee were aware of. Several cases have occurred in Australia, Sweden and the Czech Republic. Iceland has one of the smallest gene pools and has been unlucky enough to have imported several carriers, to the point that in the period 2002-2003 there were instances of more than 50% of many litters being born affected. It seems to imply that the condition is more widespread that first though as more people come to recognise the symptoms.

Several theories have been suggested, but the most practical seems to be that the condition is inherited, probably by as simple autosomal recessive gene. This means that a percentage of the Cavalier population may be carriers and when two carriers come together and affected puppy could be seen. One would expect this to be in the ratio of one affected, two carriers and one clear. However, there have been numerous cases were half or nearly all of one litter have been affected. It is not yet known whether this is just co-incidence or some other form of inheritance at work. What has been established however is that in an affected puppy's pedigree, a suspected carrier is always identified on both the sire and dam's lines. It would seem that an affected puppy is more likely to be seen where line or inbreeding on carrier lines is carried out.

There is now sufficient pedigree data available and a genetic programme is being carried out by Dr Kathryn Mellersh, a well respected geneticist at the AHT. Twenty seven (27) candidate genes have been identified and the tests are currently in progress and final results are pending.

With written support from the CKCS Club an application was made the Kennel Club for a grant to help with the research into this condition. I am pleased to report that a grant of £4,200 has been approved by the Charitable Trust and payment has been made to the AHT.

This condition is not as widespread as some other health issues but is particularly nasty in its expression. There is no treatment for the condition, only symptom and pain relief management. It is considered by the researches to be a condition best dealt with by euthanasia as soon as it is recognised. I urge all breeders to make themselves familiar with the condition to prevent unnecessary suffering to afflicted puppies.

MULTIFOCAL RETINAL DYSPLASIA (MRD)

At the 2006 Championship show, 74 Cavaliers were examined by Mr Ian Mason; very encouragingly only one case of MRD was identified. Whether this is affected by breeders obtaining litter screening results and only offering "passes" for inspection is unknown, but over the last few years there seems to be evidence of decreasing level of ocular disease. This is very satisfactory for the breed and is a fair reflection of the efforts made by conscientious breeders to avoid producing abnormalities.

Dr Keith Barnett is continuing his research at the AHT into MRD. He suspects that the gene responsible for MRD in Golden Retrievers could be the sane as the one in Cavaliers. The AHT has received a substantial grant from the Kennel Club for research in canine ocular disease and have been successful in 2005 in identifying several genes responsible for hereditary ocular disorders in other breeds. To date they believe that they have identified the chromosome responsible for MRD but are still searching for the gene. Interestingly Leeds University is researching Genetical Retinal Degeneration in humans and it is believed to be the same gene responsible for congenital cataracts in Cavaliers and Miniature Schnauzers.

DNA was sourced from and expended parti-colour family and also a whole-colour family last year. This consisted of MRD affected Cavaliers, the parents and siblings, however Dr Barnett still needs more DNA. Ideally from 4-6 affected Cavaliers and their immediate family, if anyone can help please contact Dr Keith Barnett at the AHT.

What causes it?
Syringomyelia is a consequence of an obstruction to cerebrospinal fluid (CSF) flow. In the normal mammal, the CSF around the brain shunts back and forth with the arterial pulse. If this rapid efflux and influx is obstructed then the pressure wave is transmitted down the spinal cord distending it below the blockage. This results in the formation of a cavity or syrinx. Syringomyelia can occur from any blockage in the subarachnoid space (space containing CSF around the brain and spinal cord). However, the most common cause is the cerebellum within the foramen magnum (i.e. the back of the brain poking though the hole at the back of the skull). The cerebellum is pushed (herniated) out the skull because there is not enough space since the volume of the back of the skull (occipital bone) is too small. This condition occurs in many small breeds but is common in the cavalier King Charles spaniel (CKCS) (conservative estimates at least 50% of the breed although only a proportion are severe enough to have clinical signs). It is similar to the human condition Chiari malformation (some vets refer to it as Arnold Chiari syndrome which can be confusing as the original description by Arnold was of syringomyelia associated with spina bifida and this is not the case in the CKCS).

What are the clinical signs of syringomyelia?
By far the most important sign of syringomyelia is pain. This is most commonly localised to the neck region but may be difficult to define or intermittent. Owners often report that their dog is worse at night; when first getting up; during hot or cold temperature extremes; when excited; or related to posture e.g. preferring to sleep with their head elevated. They may seem to be overly sensitive to touch on one side of the neck / ear / shoulder / sternum. In addition some affected dogs scratch at one area of the shoulder, ear, neck or sternum. This is typically one side only, while the dog is moving and sometimes without making skin contact Some dogs, more commonly younger patients, develop a scoliosis (twisted spine). Some severe cases may have other neurological deficits such as fore and hindlimb limb weakness and ataxia (wobbliness). Facial nerve paralysis, deafness and seizures have also been associated with the condition but a link has yet to be proven.

What age of dog is affected?
Clinical signs of syringomyelia secondary to occipital hypoplasia are usually recognized between 6 months and 3 years of age. However, dogs of any age may be presented and dogs with more severe disease tend to be presented before two years of age.

Do the signs get worse?
Progression of the disease is very variable. Some dogs have the tendency to scratch with mild pain only and other neurological signs, such as paresis, never or very slowly develop. Others can be severely disabled by pain and neurological deficits within 6 months of the first signs developing. A small syringomyelia may also be found as an incidental finding, with no recognised clinical signs, in the investigation of another neurological disease.

Are there any diseases with similar signs to syringomyelia?
The main diseases to rule out are other causes of neck pain e.g. disc disease (uncommon in dogs less than two years of age); CNS inflammatory diseases and other malformations. If scratching or face rubbing is the main sign then skin disease should be eliminated.

How do I know if my dog has Syringomyelia?
The only way to confirm a diagnosis is by MRI (Magnetic Resonance imaging). This is essentially a picture of the water content of the body presented in a series of slices (like a loaf of bread). Nervous tissue, which contains a lot of water, is not imaged by x-rays but is shown in great detail by MRI. The syringomyelia can be easily visualised as a pocket of fluid within the spinal cord. In severe cases the syrinx is so wide that only a thin rim of spinal cord remains

If my dog has been diagnosed with Syringomyelia what are the options?
No one can make the decision for you about what is best for your dog.

Medical management
Long-term studies of medical management of syringomyelia are not available yet. The drugs used to treat syringomyelia can be divided into 3 types:

analgesics;drugs which reduce CSF production;
corticosteroid

Analgesics
Pain in mild cases may be controlled by non steroidal anti-inflammatory drugs (NSAIDs) e.g. Rimadyl and Metacam. In more severe cases anticonvulsants, which have a neuromodulatory effect on hyperexcitable damaged nervous system, may be useful, for example gabapentin (Neurontin Pfizer;- these are not licenced for dogs). Oral opioids, e.g. pethidine or methadone are also an alternative.

Drugs which reduce CSF production
Proton pump inhibitors such as omeprazole (Losec or Prilosec) can inhibit cerebrospinal fluid formation and therefore may be valuable; clinical data on their use and effectiveness for SM is currently lacking. This drug is unlikely to be useful in the long term as therapy longer than 8 weeks duration is not recommended as this may increase the risk for stomach cancer. Carbonic anhydrase inhibitors such as acetazolamide (Diamox; Lederle laboratories) also decrease CSF flow and may also be helpful in treating syringomyelia although adverse effects of abdominal pain, lethargy and weakness may limit long term use.). Furosemide also decreases intracranial pressure and therefore could be useful in the treatment of syringomyelia.

Corticosteroids
Corticosteroids are very effective in reducing both pain and neurological deficits although the exact mechanism is not known. It has been suggested that these drugs reduce CSF pressure however laboratory evidence of this is lacking. They possibly have a direct effect on pain mediators such as substance P. Although corticosteroids may be effective in limiting the signs and progression, most dogs require continuous therapy and subsequently develop the concomitant side effects of immunosuppression, weight gain and skin changes. If there is no alternative then the lowest possible dose that can control signs is used. Alternate day therapy is preferred.

Surgical management
Surgical management is indicated for dogs with significant pain or with worsening neurological signs. The aim is to restore CSF dynamics and if this can be achieved then the syrinx can resolve. The most common procedure for Chiari like malformation is suboccipital decompression where the hypoplastic occipital bone and sometimes the cranial dorsal laminae of the atlas are removed (with or without a durotomy) to decompress the foramen magnum. The success reported in the small case series varies from no improvement to post operative resolution of the syrinx. Syringosubarachnoid shunting has also been described. In the author's experience surgery is usually successful at significantly reducing the pain but some dogs may still show signs of discomfort /scratching. Also in the author's experience signs may recur in a proportion of dogs after several months/years. One must weigh the risks and benefits of surgery versus medication versus no intervention. Remember, progressive disease means that no action may enable further deterioration.

When to have surgery?
There is more chance of success if the surgery is done early in the course of the disease before permanent damage has occurred. Surgical management is indicated for dogs with significant pain or with worsening neurological signs.

What are the risks of surgery?
There are major blood vessels in the area and if traumatised the dog could quickly bleed to death. Although not actually operating on the brain/spinal cord, it is in close proximity and there is a risk of permanent neurological injury. In reality complications from surgery seem to be rare.

Can the disease recur?
In the authors' experience signs may recur in a proportion of dogs after several months/years due to redevelopment of syringomyelia. The newly created "space" from surgery may fill in with scar tissue. If this happens, repeat surgery may be indicated; some owner prefer to continue with medical management e.g. with frusemide, NSAIDs, gabapentin or corticosteroids.

What post surgery drug treatment would you advise?
Dogs are hospitalised until comfortable enough for morphine-like-drugs to be discontinued and then discharged on a combination of non steroidal anti-inflammatory drugs (e.g. Rimadyl) and gabapentin (Neurontin). This is withdrawn when the dog is comfortable (about 2 weeks in most

Many diseases, such as Mitral Valve Disease and Syringomyelia, are believed to be inherited in the Cavalier King Charles Spaniel.

At the moment there is no way of telling which dogs will remain completely clear of these problems or which dogs, although showing no symptoms themselves, may pass on the problem to their offspring. The best way to identify carrier or clear dogs for both conditions is to develop a gene test, and for this researchers need blood from extended families of cavaliers.

The Cavalier Club have a Healthy Heart Partnership with the pharmaceutical company, Boehringer Ingelheim, and thanks to their financial support, we help to set up a project to collect and store cavalier blood for DNA extraction. The confidential project was planned and coordinated by a veterinary neurologist, Dr Clare Rusbridge, and the Club Research Fund paid for blood collection costs from selected cavaliers.

The Cavalier Club also organised blood donor sessions at health clinics & shows and we are very grateful to our members who attended with their cavaliers, to those owners who paid their own costs to provide blood samples, and the vets who supported the scheme by charging a reduced fee for their services.

The project could not have been undertaken without the support of the UK DNA Archive for Companion Animals, which provided DNA extraction and storage from samples taken in the UK.

Dr Rusbridge, and her researcher Penny Knowler, spent hundred of hours working in their own time arranging DNA collection and collating information for the scheme. Thanks to their efforts DNA has been collected from Cavaliers all over the world. Cavalier owners and breeders owe them an enormous debt of gratitude.

The first stage of the project is now complete and Clare, Penny and their Canadian collaborators, Guy Rouleau and Berge Minassian, have been successful in applying to the Mammalian Genotyping Service at the Marshfield Clinic in Wisconsin (USA) for a full genome scan. The research is initially into syringomyelia but hopefully will be extended to looking for candidate genes for MVD as well.

Syringomyelia is a painful condition that also affects people. The research, undertaken by a joint veterinary and human medical group, will benefit both 'man and his best friend'. The researchers say that many people worldwide will benefit from this research.

The genome scan will identify markers which can then be used to identify the gene/s responsible for the disorder causing syringomyelia. The same team have already been successful in identifying the canine gene for Lafora's disease. The research is expected to take several years but the first stage will hopefully produce a DNA test which will help owners to make informed breeding decisions.

The researchers say that due to the generosity of clubs, research projects and individuals, they have collected enough DNA samples to start the genome scan. They therefore no longer require DNA from cavaliers with syringomyelia.

They do need blood samples from:-

Episodic Falling (EF) is a syndrome of muscle stiffness or collapse that occurs in the Cavalier King Charles Spaniel. It has been in evidence in the Cavalier for over forty years and the number of reported cases has shown a dramatic increase over the last few years. The more correct medical terminology to describe the syndrome is that of ‘Paroxysmal Exercise-Induced Dystonia’, and forms part of a group of so-called Movement Disorders recognised in dogs, but the terms Episodic Falling and Hypertonicity have become accepted to describe the condition.

The South and West Wales CKCS Club is supporting the research being carried out into Episodic Falling.

RESEARCHERS

Dr Jacques Penderis BVSc, MVM. PhD, Cert VR, DipECVN, MRCVS, RCVS and European Specialist in Veterinary Neurology is leading the research.

Dr Penderis has, almost single-handed, been researching this condition for a number of years with extremely limited funds. He is now working with Dr Cathryn Mellersh PhD, Head of the Genetic Department at the Animal Health Trust in Cambridge.

Dr Mellersh has managed to secure funds to employ a full time student, Oliver Foreman, to work on three canine neurological disorders at the AHT, one of which will be Episodic Falling in Cavaliers.

Dr Penderis, Dr Mellersh and Mr Foreman will also be working with Professor Robert Harvey (Neuro-science and Genetics) from The School of Pharmacology.

Professor Harvey is working on Hyperkplexia, a human disorder for which he has found new genes that could be related to EF, hence his interest in the CKCS. This is very exciting and could be a major breakthrough.

INITIAL WORK

The initial analysis work and sequencing of the genes will be done at The Animal Health Trust. If the candidate genes proposed by Professor Harvey are involved, the work will continue at his laboratory. If the genes are different then an SNP chip (geonome scan) will be run on 40 dogs, which is all they can afford to do at the moment.

Jacques Penderis and his team have a very good track record and have recently isolated the gene that causes L-2-HGA (L-2-hydroxyglutaric aciduria), a nuerometabolic disorder in Staffordshire Bull Terriers. They now have a DNA test available for this disorder.

FUNDING

The team have been unable to secure funding for the initial work, which will cost about £2000 or for the SNP chip which will be £6,000 ($12,000). They are hoping that Cavalier clubs, owners and breeders will be able to help with donations or fund raising.

So please consider sending what you can towards the cost of this research, every little helps. We are very lucky to have these top neurologists and geneticists giving their time to this study,

Donations can be sent to Dr Cathryn Mellersh, The Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk. CB8 7UU
Email: Cathryn Mellersh

Cheques should be made payable to The Animal Health Trust but please include a covering letter stating that the donation is for Episodic Falling in the CKCS research. This will ensure that it is paid into the correct account.