Dr. Clare Rusbridge, a European Specialist in Neurology, has initiated a DNA Blood Collection Project on an international level. Dr. Rusbridge has written two research papers on this disorder and both were published in the American Journal of Veterinary Medicine. Reprints are available from her associate, Penny Knowler, with proceeds to go towards SM research. This project is supported by the Cavalier Club in the UK and is partially funded by a grant from Boehringer Ingelheim. All DNA/Blood is now being centralized at the McGill University Health Centre in Montreal, Quebec - Canada with Dr. Guy Rouleau as the principal investigator. Dr. Rouleau and his Canadian team will be analyzing the data collected.

Due to the wonderful insight from committed owners, breeders and veterinarians from around the world, amazing progress has already been made. Updates are available from the UK website: http://www.thecavalierclub.co.uk and will also be posted to our Canadian National website: http://www.cavaliercanada.com. As we receive new updates we will also be publishing them in our bi-monthly news "Quotes" which is mailed to our members.

Although it appears this condition has been around for a number of years, it is only recently that active research has begun. The Cavalier King Spaniel Club of Canada, Health and Education Committee, has been actively addressing this recently diagnosed condition by publishing articles in our club's Quotes Newsletter on an ongoing basis. Because DNA collection (blood) is what the researchers are requesting at this time and because we wish to show our support for Dr. Rusbridge's research project, this committee did undertake the task of organizing our first DNA Blood Collection clinic - held on December 12, 2004 at the Graham Animal Hospital, Hillsburgh, Ontario - just west of Toronto. An email was sent to those members considered to be within driving distance. See Cavalier Central homepage for specific details at http://www.cavaliercanada.com. Our first effort was a huge success and our goal to have in excess of 26 donors (who have fallen into the most desirable category) of target cavaliers was exceeded as we had 32 donors. Target dogs are:

- Cavaliers that are symptomatic for the following diseases and their immediate relatives sire, dam, siblings and offspring:

Syringomyelia - symptoms of Syringomyelia vary – they can be mild or severe –see the Club information sheet (with or without MRI results)

MVD less than 5 years and/or their immediate relatives

Epilepsy

- Top winning/producing Dogs and Bitches that frequently appear in pedigrees

- Cavaliers 7 years and over with "clear" hearts (either a board certified Cardiologist or a general practitioner veterinarian evaluation qualify)

In addition to meeting the above qualifications, participants will also be required to provide the following supporting documents:

- Phenotype Form (with "Consent" at bottom of page);

- 5 generation pedigree

- Any supporting medical records that may be available (eg MRIs, cardiologist reports, vet reports)

Those wishing to participate in Dr. Rusbridge's DNA Blood Collection project may do so either through a sponsored/organized clinic or by acting independently through their own veterinarian. The appropriate and necessary forms are available through this website: http://www.candog.com/cavaliers/ or by requesting information and obtaining such forms from our designated Canadian contact person - Pat Barrington (Chairperson of the Health and Education Committee of the Cavalier King Charles Spaniel Club of Canada), at: harley2@sympatico.ca These forms can be emailed to you. These forms are also available in a downloadable format from the UK website; however some of the information on these forms is not relevant to Canadian use.

Regional Cavalier Clubs are encouraged to hold a clinic in their area. The Health and Education Committee is more than willing to offer guidance.

Special thanks to Dr. Carol Graham and Dr. Alison Jones who have agreed to donate their veterinary facility, as well as the donation of Dr. Jones' time and service to conduct a brief examination attending to symptoms for Syringomyelia and performing an auscultation re: MVD and to Lisa Lott (vet-technician) who has also agreed to donate her time and service in memory of her cavalier. It is important to mention that this blood draw will address DNA research for more than that of Syringomyelia. This blood draw will also provide DNA information for research towards MVD and epilepsy.

Syringomyelia

By: Clare Rusbridge BVMS DipECVN MRCVS

What is Syringomyelia?

Syringomyelia (SM) is a progressive neurological disease that varies in severity. Some refer to SM as "neck scratcher's disease" because scratching in the air near the neck is often a sign of the disease, especially when on a leash. It is similar to the human condition, Chiari type 1 malformation (or Arnold Chiari in some older texts).

What causes it?

It is typically due to occipital hypoplasia (malformation of the bone at the back of the skull which is too small). The smaller sized bone changes the shape of the skull so that the brain is squashed inside. The cerebellum (part of hind brain which co-ordinates movement and balance) is forced into the foramen magnum (small opening at the back of the skull which leads into the spinal cord) is kinked. Cerebrospinal fluid, which is around the brain and spinal cord, moves back and forth through the foramen magnum with the arterial pulse and with changes in chest or abdomen internal pressure (e.g. barking). When there is occipital hypoplasia the foramen magnum is obstructed, the fluid cannot move to and fro easily and is forced into the spinal cord creating a cavity or cavities (syrinxes) resulting in the condition called syringomyelia. Since it was caused by occipital hypoplasia, it is referred to as ‘Syringomyelia secondary to occipital hypoplasia'. Most cavaliers have a degree of occipital hypoplasia but they don't all get syringomyelia.

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 visualized 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.

What clinical signs can the vet look for if I choose not to have an MRI?

Typically clinical signs are only seen when there is syringomyelia. The damage to the spinal cord and the interruption of CSF flow results in pain and abnormal sensations of which the most common signs are crying and shoulder scratching, especially when excited or walking on a lead. The scratching is usually to one side but may become both. There is not evidence of skin or ear infections. Unlike scratching for skin disease the dogs often walk and scratch at the same time and make little contact with the skin.

Affected dogs are also sensitive around the head, neck and forelimbs. They often cry/yelp/scream for apparently no reason (some of these dogs may have unfair reputations for being a baby). Pain may be related to head posture and some dogs prefer to sleep or eat with their heads up. Excitement, barking, coughing, suddenly rising or exertion can increase the fluid pressure in the syrinxes and precipitate the scratching and/ or crying. Some severely affected young dogs develop a neck scoliosis i.e. their neck is twisted. Other affected dogs may develop a wobbling hind limb gait (pelvic limb ataxia) and/or a forelimb weakness (thoracic limb weakness). Signs are usually recognized between 6 months and 3 years however dogs of any age may be presented. Mildly affected dogs may only have occasional signs of pain.

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

Medical management can help but typically does not resolve the clinical signs. Signs in mild cases may be controlled by non steroidal anti-inflammatory drugs (Naiads) e.g. Rimadyl. Corticosteroids are very effective in reducing signs partly because of the effect on reducing CSF pressure and possibly because of a direct effect on chemicals which mediate pain. Although corticosteroids are effective in limiting the signs 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 use the lowest possible dose to control signs. For a CKCS the typical dose would be 5mg prednisolone or 4mg methylprednisolone daily/on alternate days. Gabapentin (Neurontin; Pfizer) is successful in some dogs. This drug, originally patented as an anticonvulsant, is licensed as a neurogenic analgesic for humans. Gabapentin, and other anticonvulsants suppress the firing of hyper excitable damaged nervous system. The canine dose is 10-20 mg/kg two/three times daily which for a CKCS typically works out at a dose of 100mg two/three times daily. Gabapentin can also be given in combination with NSAIDs. Sedation may be seen, especially at higher does, otherwise the side effects are minimal and on this basis the authors' prefer Gabapentin over corticosteroids. The main disadvantage of Gabapentin is that it is expensive and not licensed for dogs. Oral opioids are also an alternative for example pethidine tablets at 2 – 10mg/kg three to four times daily or methadone syrup at 0.1 – 0.5mg/kg three to four times daily. Acupuncture appears to help some dogs.

Surgical management

SM is a surgical disease – the most appropriate management is to open the foramen magnum by removing a portion of the occipital bone and usually part of the first vertebrae (foramen magnum decompression surgery). The aim of surgery is to reduce the pain improving the dog's quality of life and/or to stop or reduce further progression. If neurological damage has already occurred, the surgery may not reverse the damage and most dogs still have a tendency to scratch.

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 measuring the surgery's success, measure from current condition to the expected further condition – what the disease would have progressed to, rather than the current condition only.

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. Surgery is recommended for dogs with signs at less than 5 years old because progressive disease is likely. In older dogs surgery is advised if the dog is deteriorating.

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 owners prefer to continue with medical management e.g. with NSAIDs, Gabapentin or corticosteriods.

What post surgery drug treatment would advise?

Dogs are hospitalized 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 cases).

DNA collection program

Our aim is to provide a comprehensive, integrated collection of Cavalier King Charles spaniel DNA for the benefit of the dogs, owners, breeders and to provide insight into human disease. Surplus blood from a health check would be stored for future studies on the health of the breed. The current studies include Syringomyelia (SM), Mitral Valve Disease (MVD) and Epilepsy.

Questions & Answers:

Why is blood needed?

It is easy to extract DNA from the white blood cells in a blood sample. To do this the blood must be fresh and prevented from clotting by putting it in an EDTA tube.

What will happen to the blood sample from a dog?

The DNA sample being submitted to the researchers will be anonymous once it is entered into the archive and will be kept strictly confidential. The samples and clinical data will be made available to bona fide research groups working on these conditions and where the projects have been deemed to be ethically sound. The owner will also retain the right to remove the sample from the archive in the future if so wished. However, no information regarding tests performed on the DNA sample will be given back to the owner. It will only be possible to find out which genes and environmental factors are important by identifying patterns in large numbers of affected and unaffected animals.

What kinds of dogs are needed to give blood?

All blood from Cavaliers will be valued. The purpose of the study is to identify a gene through DNA analysis. We are therefore focusing on certain areas to be most successful in achieving our goal. We need dogs that are:

Normal healthy, especially if over 7 years or MRI confirmed normal (no SM)

Champions that often appear in pedigrees (any age)

SM Affected – MRI confirmed or showing typical clinical signs

Parents and siblings of affected dogs

Offspring of affected dogs – IF < 3 years of age the blood may be stored in case signs develop later.

Mates of an affected dog – is helpful if DNA from offspring is collected later

MVD affected and their relatives (see SM above)

Remember

Your blood donation will help keep Cavaliers healthy from inherited diseases. SM/MVD carriers can have good genes/characteristics that we need to conserve. The more help we get the speedier will be the result.

Why do I need to provide a pedigree?

Pedigree information about your Cavalier is important for our study. The relationship between affected and non affected family members can indicate the way in which a disease can be inherited. Comparisons are made between the parental genotypes and those of the offspring. Pedigree analysis is not sufficient in itself to determine if a trait is inherited as a threshold trait. There are many investigations to be made and that is why you are asked for as much blood (DNA) as possible. Linkage may be used, which means DNA from animals that link up affected individuals would be needed. Bottom line: It is essential that we have DNA from related dogs regardless of whether their status is known.

Copyright: Clare Rusbridge BVMS DipECVN MRCVS

Disclaimer: Your veterinarian is the most qualified person to answer all of the questions you have about your pet's health. Nothing in this article should be construed as medical advice regarding any individual animal’s condition.