Episodic Falling Syndrome (Muscle Hypertonicity): Cavaliers Collapse Suddenly After Exercise
- Symptoms
- Diagnosis
- Treatment
- Current Research
- Breeders' Responsibilities
- Related Links
- Veterinary Resources
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.
Some researchers have suggested that EFS in Cavaliers may be associated with another disorder unique to the breed, called "idiopathic asymptomatic thrombocytopenia", an abnormally low number of blood platelets. Drs. Jens Häggström and Clarence Kvart of Sweden have noted in a 1997 article that thromboembolic events in the cerebral circulation of blood may be involved in EFS. See Blood Platelets for more information.
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.
In a brief July 2009 article, UK researchers Dr. Richard J Piercy and Gemma Walmsley disclosed that they had identified a genetic form of muscular dystrophy in the Cavalier, with symptoms (weakness and exercise intolerance) similar to some of those of EFS. However, these other symptoms of this muscular dystrophy may clearly distinguish it from EFS: muscle atrophy, difficulty swallowing, and an enlarged tongue. Also, the researchers have found that only males are affected by this form of muscular dystrophy, and the females are only carriers of the mutation.
Treatment
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.
In cases that do not respond to clonazepam and where the episodes are not particularly severe or frequent, it may be best to accept the collapse episodes and try to identify and avoid events or stressors that may trigger the episodes. In severe cases, treatment can be tried with acetazolamide (Diamox), which is a carbonic anhydrase inhibitor which has shown some efficacy in autosomal dominant hyperkalemic periodic paralysis. Use of acetazolamide must only be done under careful veterinary supervision, and a number of dogs do not appear to tolerate the drug very well.
For more advice on treatment please contact Dr. Penderis. He may be contacted at Clinical Neurology / Neurosurgery Service, Faculty of Veterinary Medicine, University of Glasgow, Bearsden Road, Glasgow G61 1QH, Tel: +(44) 0141 330 5738 (office), Email: j.penderis@vet.gla.ac.uk
Current Research
4April 2009: Dr. 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 reports that funding is now in place to perform a genome scan in the Cavalier to try and identify the genetic region of interest responsible for episodic falling. Funding is still required for the fine sequencing to follow the genome scan. Anyone interested in contributing to these projects should contact Dr. Cathryn Mellersh at the Animal Health Trust, email: Cathryn.Mellersh@ aht.org.uk
For this study Dr. Penderis is very interested in collecting blood samples or cheek swabs for DNA extraction from affected dogs, and normal related dogs. 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 Clinical Neurology / Neurosurgery Service, Faculty of Veterinary Medicine, University of Glasgow, Bearsden Road, Glasgow G61 1QH, Tel: +(44) 0141 330 5738 (office), Email: j.penderis@vet.gla.ac.uk
4October 2007: Dr. Penderis reported 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.
Related Links
Questions for Breeders
Blood Platelets
Syncope
An excellent website to learn more about Cavaliers with episodic falling
syndrome is
Cavalier Episodic Falling
Veterinary Resources
Episodic falling in the Cavalier King Charles spaniel. Herrtage ME, Palmer AC. Veterinary Record 1983;112:458-459.
Muscle hypertonicity in the cavalier King Charles spaniel - myopathic features. Wright JA, Brownlie SE, Smyth JBA et al. Veterinary Record 1986;118:511-512.
A myopathy associated with muscle hypertonicity in the Cavalier King Charles Spaniel. Wright JA, Smyth JBA, Brownlie S, Robins M. J Com Path 1987;97:559-565. Quote: "Clinical signs of electrically silent muscle hypertonicity are described in five Cavalier King Charles dogs. Biopsies of the biceps femoris and triceps muscles, when examined with the electron miscroscope, revealed evidence of sarcotubular and mitochondrial abnormalities. These included enlargement of the sarcoplasmic reticulum, hydropic degeneration of mitochondria, tubular proliferations in the vicinity of the triads and vacuolar invagination of mitochondria. The exact nature of these findings is not clear and it is suggested that utilization of tracer techniques would help to explain them."
Low cerebrospianl fluid concentration of free gamma-aminobutyric acid in startle disease. Dubowitz LM, Bouza H, Hird MF, Jackson J. Lancet 1992;340:80-81. Mutations in the alpha 1 subunit of the inhibitory glycine receptor cause the dominant neurologic disorder, hyperekplexia. Shiang R, Ryan S, Ya-Zhen Z et al. Nature Genetics 1993;5:351-358.
Update on Mitral Valve Disease. Jens Häggström and Clarence Kvart. Proc. 15th ACVIM Forum; 1997. Quote: "An interesting observation that may be of comparative interest is that Cavalier King Charles Spaniels have been shown to have a high prevalence (30%) of thrombocytopenia and macrothrombocytosis. Humans with MVP [mitral valve prolapse] tend to have shortened platelet survival times and thromboembolic episodes primarily in the retinal and cerebral circulation. Thromboembolic events in the retinal ore cerebral circulation may be involved in the disturbances described in the breed as 'episodic falling' and 'fly catching'."
Control of Canine Genetic Diseases. Padgett, G.A., Howell Book House1998, pp. 198-199, 234.
Hypertonicity in Cavalier King Charles Spaniels. Shelton GD, Comparative Neuromuscular Lab, June 2001.
Muscular dystrophies and other inherited myopathies. Shelton GD, Engvall E,Vet Clin North Am Small Anim Pract 2002; 32:103-124.
Hypertonicity in Cavalier King Charles Spaniels. Garosi LS, Platt SR, Shelton GD, J Vet Intern Med 2002; 16:330.
Clinical Neurology in Small Animals - Localization, Diagnosis and Treatment. K.G. Braund, International Veterinary Information Service, Ithaca, New York, USA; Paroxysmal Disorders (6-Feb-2003). Quote: "Episodic falling or hypertonicity is a well-recognized paroxysmal disorder in Cavalier King Charles Spaniels in the UK, and has been seen in the United States and Australia." www.ivis.org/special_books/Braund/braund29/ivis.pdf
Breed Predispositions to Disease in Dogs & Cats. Alex Gough, Alison Thomas. 2004; Blackwell Publ. 44-45.
Neurological diseases of the Cavalier King Charles spaniel. Rusbridge, C. J Small Animal Practice, 30 June 2005, 46(6): 265-272.
Muscular dystrophy in Cavalier King Charles spaniels. Piercy, Richard. J. and Walmsley, Gemma. Vet Rec. 2009 165 (2), p. 62. Quote: "We have recently identified the genetic cause of a form of muscular dystrophy in CKCS. The causative mutation is in the dystrophin gene and the X-linked disease is associated with weakness, muscle atrophy and exercise intolerance, detectable from a few months of age. Prominent signs in affected dogs are dysphagia [the symptom of difficulty in swallowing] and macroglossia (enlarged tongue)[tongue enlargement that leads to functional and cosmetic problems]. Serum creatine kinase is usually markedly elevated. Male dogs with the mutation [are] clinically affected and female dogs with the mutation are silent carriers. We are also keen to hear from veterinary surgeons who believe they may have seen an affected dog in their practice, in order to estimate the prevalence of this disease and limit its spread by genetic testing." Contact Dr. Piercy at the Royal Veterinary College's Comparative Neuromuscular Diseases Laboratory at rpiercy@rvc.ac.uk
