Episodic Falling Syndrome and the Cavalier King Charles Spaniel

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Episodic Falling Syndrome (Muscle Hypertonicity):

Cavaliers Collapse Suddenly After Exercise

Episodic falling syndrome (EFS) is a unique genetic disorder in the Cavalier King Charles spaniel. It has been recognized in the breed since the1960s. No other breed is known to suffer from it. Veterinarians may refer to it as hyperexplexia or muscle hypertonicity (and medically known as "paroxysmal exercise-induced dystonia"). It appears to be a life-long condition of the Cavaliers affected by it, but it rarely is life-threatening.

Symptoms

Symptoms of EFS vary, but they all are attributed to the dog’s muscles being unable to relax. Typical signs include the Cavalier engaged in exercise or being excited or stressed, and then suddenly develop a rigid gait in the rear limbs, extending and retracting in an exaggerated, stiff manner, like that of a hopping rabbit. The dog’s back may be arched, and the dog often yelps. One or more limbs may also protract excessively. The dog may lose its footing while running. It usually loses all coordination and collapses on its side or on its face. When the Cavalier collapses, it may hold its forelegs over its head.

In some instances, the Cavalier’s symptoms follow a “deer-stalking” behavior, with its head held close to the ground and its rear high in the air, as if stalking game. In the most severe cases, the dog may hold its head so low that its hind quarters somersault over its head. The affected Cavalier may exhibit these symptoms only when excited or stressed, but in some cases, the behaviors have not been stress-induced.

The Cavalier does not lose consciousness during the episodes, and mentally, it remains normal. Technically, the collapse is not a seizure, although it may be appear as one. The CKCS appears to know what is happening to it, and sees clearly, but loses control of its body. Afterwards, in most instances the dog recovers relatively quickly; it stands up and acts as if nothing unusual had occurred. However, if the Cavalier exercises again immediately after recovery, it may induce another episode.

Also, some severely affected Cavaliers have been known to lapse into repeated, lengthy episodes of the syndrome, and may even suffer permanent neurological injuries and not be able to recover from the attacks. At least a few CKCSs are known to have been euthanized to avoid continued suffering from the disorder.

It is to be distinguished from presyncope, another disorder to which Cavalier King Charles spaniels are predisposed, which has some of the same symptoms. Syncope in Cavaliers is associated with late stages of mitral valve disease. For more information on syncope and presyncope in CKCSs, see Mitral Valve Disease and Syncope.

Diagnosis

Episodic falling syndrome appears to be a type of metabolic muscle disorder. The ages of Cavaliers studied with EFS have varied from two months to four years. Both male and female CKCSs are affected.

There are no tests for diagnosing EFS. There is no known clinical or pathological abnormality or neurological problem to account for the behavior. The dogs are neurologically normal between episodes. Electromyographic evaluation detects the muscles at rest and engaged in no abnormal spontaneous activity. There is no evidence of heart or respiratory problems during the episode or the collapse. Blood tests, spinal fluid analysis, muscle biopsies, and magnetic resonance imaging (MRI) of the brain have not proved to be helpful in diagnosing the syndrome. Diagnosis, therefore, is based solely upon the symptoms of the episode.

Since some of the symptoms of EFS are similar to other disorders, such as liver shunt, an epileptic seizure, or syringomyelia, the examining veterinarian may mis-diagnose the episodes and unnecessarily screen the dog for those other maladies. The primary differences between EFS and other disorders are that they usually are induced by exercise, excitement, stress, or apprehension; the EFS-affected dog remains conscious during the episodes; and the dog rarely will experience any continuing pain or discomfort.

Therefore, video recordings of the dog’s EFS episodes are helpful to the veterinarian in diagnosing the disorder. If a video device is not available, the owner should write a precise report of the Cavalier’s behaviors during the episode, to avoid mis-diagnosis, needless testing, and treatment with drugs which may inadvertently aggravate the condition.

Treatment

CavalierHealth.org Copyright © 2004 Blenheim Company Until recently, no medications appeared to remedy the condition, and there was no known effective treatment. Affected dogs have not been found to respond to anticholinesterases. Phenobarbital (Solfoton), a barbiturate, frequently is prescribed.

Some temporary improvement has been observed following treatment with a benzodiazepine drug called diazepam (Valium). In a study concluded in 2003, a group of affected Cavaliers was treated with another benzodiazepine drug, clonazepam (Klonopin, Rivotril), which is a drug used to treat humans for hereditary hyperexplexia or hyperekplexia ("startle disease"). Both diazepam and clonazepam enhance GABA neurotransmission. However, clonazepam is more potent than diazepam in equivalent doses, and clonazepam has more anti-convulsant effects. In the 2003 study, with clonazepam treatment (at 0.5 mg/kg tid), the episodes decreased in frequency from between 25 and 30 per week to as few as one every two to three months. After two years of treatment with clonazepam, dogs in the study were described as clinically normal.

In a study currently being conducted by Dr. Jacques Penderis (formerly a senior research neurologist at the Animal Health Trust in the UK and now at the University of Glasgow), he has found that although some Cavaliers initially respond well to treatment with clonazepam or diazepam, the dogs tend to develop tolerance to the drugs after a while and the beneficial effect wears off. Dr. Penderis states that the current treatment options for CKCSs with episodic falling syndrome are extremely limited.

Current Research

4Dr. Penderis is conducting research to try to establish the pattern of inheritance of episodic falling in the Cavalier. He is collecting pedigrees from affected dogs for pedigree analysis, particularly where the disease status of related dogs (e.g. parents and litter mates) are known. He is examining two genes, and he has applied for a grant to run a full genome scan.

In an attempt to develop a more effective treatment for dogs that are severely affected, Dr. Penderis is conducting a trial of some other drugs that have been shown to be beneficial in human patients and to which the Cavaliers' tolerance does not develop. He advises that the initial results for one drug have so far been promising. The current trials are restricted to those dogs that have very frequent collapse episodes and are arranged through the owners' veterinarians.

Dr. Penderis also is collecting blood samples for DNA extraction to conduct genetic linkage analysis in order to determine the offending genes. In order to perform genetic linkage analysis, Dr. Penderis requires blood samples from known affected dogs and from as many normal related dogs as possible (particularly litter mates, parents, grandparents and offspring). The study's goal is to develop a genetic test to allow identification of the affected dogs and asymptomatic carriers, so that the disease may be totally eradicated from all tested breeding lines. Dr. Penderis may be contacted at Episodic Falling Research, Faculty of Veterinary Medicine, University of Glasgow, Bearsden Road, Glasgow G61 1QH, Tel: +(44) 0141 330 5738(office) or +(44) 0141 330 5848 (receptionist); Fax: 0141 330 3663; Email: j.penderis@vet.gla.ac.uk

4Dr. Penderis reported in October 2007 that he has teamed up with Dr. Cathryn Mellersh of the Animal Health Trust and a graduate student, Oliver Forman, to conduct a study of four canine neurological conditions, including episodic falling in the CKCS. Also, Professor Robert Harvey, of The School of Pharmacy in London. has proposed some "interesting candidate genes" for the Cavaliers they we will be jointly studying.

These candidate gene studies are in need of financial underwriting. Dr. Penderis estimates that it will cost £2,000 +/- for the candidate gene work, and there will be the sequencing costs to follow that, in excess of £6,000. Anyone interested in contributing to these projects should contact Dr. Cathryn Mellersh at the Animal Health Trust, email: Cathryn.Mellersh@ aht.org.uk

Breeders' Responsibilities

No Cavalier King Charles spaniel which has experienced episodic falling syndrome should be bred. Cavaliers which have parented affected offspring should not be bred without consultation with a veterinary specialist in episodic falling syndrome.