Exercise-induced collapse (EIC)

Research to investigate and characterize EIC in Labrador retrievers has been led during the last decade by a team at the WCVM (Drs. Taylor and Shmon). They collaborated with a team of veterinarians and geneticists at the University of Minnesota (Patterson, Mickelson, Minor). In 2007,  the genetic mutation causing EIC was identified and a test for the causative mutation was made available through the Veterinary Diagnostic Laboratory at the University of Minnesota.

This is important information to have about a dog prior to breeding so that a breeder can avoid producing dogs affected by EIC.

• If an affected dog is bred to another affected dog all offspring will be affected.
• If an affected dog is bred to a carrier dog, 50 per cent of offspring will be affected and 50 per cent will be carriers.
• If an affected dog is bred to a clear dog, all the offspring will be carriers.
• If a carrier is bred to a carrier, approximately 25 per cent of the puppies will be clear of the mutation, 50 per cent will be carriers and 25 per cent will be affected by EIC.
• If a carrier is bred to a non-carrier, none of their pups will be affected, but 50 per cent will be carriers.

Not all dogs affected by EIC (two copies of the mutation) will have had episodes of collapse. Approximately 85 per cent of affected dogs have collapse observed by the time they are three years of age, but some affected dogs never exercise with the intensity and excitement required to induce an episode of collapse.

Without genetic testing it is impossible to say for certain that a dog is not affected by EIC.

The EIC mutation is common in populations of the susceptible breeds. In the populations of dogs tested:

• 5-15 per cent of Labrador retrievers have been affected, and 35-40 per cent have been carriers
• 2-3 per cent of Chesapeake Bay retrievers have been affected, and 15-20 per cent have been carriers
• 15-20 per cent of Curly Coated retrievers have been affected and 30-35 per cent have been carriers.

Testing for EIC involves the collection and submission to the laboratory in Minnesota of an oral swab for DNA. This should be done by a veterinarian. The veterinarian will also verify the identity of the dog being tested (microchip or tattoo) for the laboratory.  

All results are eligible for posting on the Orthopedic Foundation for Animals (OFA) website for a nominal charge with owner consent. For more information about EIC and the test, visit the U of M's Veterinary Diagnostic Laboratory.

Owners who would like to have their dog tested for EIC at the WCVM should do the following:

• Make an appointment with the Small Animal Medicine service for DNA testing.
• Go to the EIC website. Click on the submission form option, fill out the form online and print it to bring with them to their appointment.  Filling out the form online minimizes the chance that there will be typographical errors in your dog's information when we submit a handwritten form to the laboratory with the sample.
• You must pay the Minnesota laboratory directly for the testing (not the WCVM). If you wish to pay for the test by credit card, fill out the credit card authorization form that is attached to the submission form and bring that with you to the appointment.
• If you do not wish to pay by MasterCard or Visa, you will need to bring a money order or certified cheque for $65.00 US (made out to the Veterinary Diagnostic Laboratory, University of Minnesota) to the appointment so that we can enclose it in the sealed envelope with the sample.
• Do not give your dog anything to eat or drink (except water) for four hours before your appointment.
• During the appointment:
  • A veterinarian will collect a history and examine your dog. If your dog is due for routine procedures such as annual examination or vaccination, these can be completed during the same visit.
  • Your dog's permanent identity will be verified (microchip or tattoo) if possible. If your dog has a tattoo please bring a copy of their CKC or AKC registration papers stating the tattoo number for your dog in case one of the letters/numbers is difficult to read.
  • We will perform the DNA swabs, fill out the required forms and seal the samples in envelopes according to directions from the laboratory.
  • We will give you the samples in a sealed, pre-addressed envelope to mail to the laboratory. We recommend mailing the EIC test via ExpressPost (Canada Post) to the Minnesota laboratory.
  • The WCVM Veterinary Medical Centre fee will be the fee for an office call plus a $35.00 DNA collection and processing fee (includes the swabs).

Dynamin-associated exercise intolerance and collapse (d-EIC) is a common inherited disorder in Labrador Retrievers. Black, yellow and chocolate Labradors of both sexes are affected. Signs first become apparent in young dogs — usually between five months and three years of age (average 14 months).

Affected dogs exhibiting symptoms of collapse are usually described as extremely fit, muscular, prime athletic specimens with an excitable temperament and lots of drive.

EIC is the most common reason for exercise/excitement induced collapse in Labrador retrievers that seem otherwise normal and healthy between collapse episodes.  

Current data from the first 45,000 Labradors tested at the University of MN (as of 10/2017) shows that nearly 40 per cent of all Labradors tested have been carriers (with one copy of the mutation: E/N) and approximately six per cent of dogs have been affected (with two copies: E/E) and susceptible to collapse. Some dogs have been tested because of collapse, but most tests have been performed to determine EIC status for breeding purposes.  Interestingly, the prevalence of carriers is not different between field trial /hunt test dogs and show dogs and pet dogs.

Most (>80 per cent) affected Labradors (E/E: two copies of the mutation) experience at least one episode of collapse by the time they are four years of age. Many competitive field trial dogs are unable to continue training and competing at a high level but if trigger activities can be avoided, dogs with EIC live normal lives. A few genetically affected (E/E) dogs rarely or never exhibit collapse, perhaps because they do not engage in the required strenuous activity with extreme excitement that is required to produce collapse. DNA testing is the only way to know for certain whether a dog has EIC.

The research laboratory at the University of Minnesota has tested  hundreds of samples from many of the other common retriever breeds including golden retrievers, flat-coated retrievers, Chesapeake Bay retrievers, Nova Scotia duck tolling retrievers and curly coated retrievers. So far, in retrievers, the mutation has only been found in Labradors, curly coated retrievers (40 per cent carriers, 18 per cent affected) and in Chesapeake Bay retrievers (17 per cent carriers, three per cent affected).

The laboratory has also tested normal and collapsing dogs from many other working and sporting breeds. The mutation has been identified in Boykin spaniels (33 per cent carriers, seven per cent affected), old English sheepdogs (30 per cent carriers, three per cent affected), and rarely in German wirehaired pointers,  Bouvier des Flanders, Pembroke Welsh corgis and cocker spaniels.

Other Collapse Disorders

Many breeds of dogs have exercise intolerance syndromes that are not caused by the DNM1 genetic mutation that causes EIC.

Our research team has been investigating a disorder called border collie collapse that affects border collies, Australian cattle dogs, Australian kelpies, Australian shepherds, Shetland sheepdogs, bearded collies, and collies. http://z.umn.edu/bordercolliecollapse

Dogs with d-EIC can tolerate mild to moderate exercise, but five to 20 minutes of strenuous exercise with excitement induces weakness and then collapse. Some affected dogs collapse whenever they are exercised to this extent — other dogs only exhibit collapse sporadically.

Typically the rear limbs become weak and unable to support weight and dogs will continue to run while dragging their back legs. Dogs develop a wide-based, long, loose stride rather than the short, stiff strides typically associated with muscle weakness. In some dogs the rear limb collapse progresses gradually to forelimb weakness and occasionally to a total inability to move. Muscles of the rear limbs are relatively flaccid during collapse and there is loss of the patellar reflex during collapse and for a short time during recovery. Some dogs appear to have a loss of balance and may fall over, particularly as they recover from collapse. Dogs are not painful or stiff during the collapse or upon recovery. A few dogs have died during or immediately after an episode of exercise-induced collapse – the reason for their death has not been determined but failure to ventilate adequately and hyperthermia have been considered most likely – post mortem evaluation is normal.

Dogs worsen after exercise
It is common for the symptoms to worsen for three to five minutes even after exercise has been terminated. A few affected dogs have died during exercise or while resting immediately after an episode of exercise-induced collapse. An affected dog's exercise should ALWAYS be stopped immediately at the first hint of incoordination or wobbliness.  

Veterinary evaluation
Nervous system, cardiovascular and musculoskeletal examinations are unremarkable at rest in dogs with EIC as is routine blood analysis at rest and even during an episode of collapse. These dogs do not experience heart rhythm abnormalities, low blood sugar, electrolyte disturbances or respiratory difficulty during collapse.  Body temperature is remarkably elevated during collapse (average 107.1F [41.7C], many up to 108F [42.2C]), and carbon dioxide levels in their blood are very low due to extreme panting to blow off heat, but the high temperatures and degree of hyperventilation are  not different from those measured in normal Labradors without EIC who perform the same exercise.

Recovery from collapse
Most dogs recover from EIC-collapse quickly and are normal within five to 25 minutes with no residual pain, weakness or stiffness. Recovery is gradual rather than instantaneous — they do not just “snap out of it." Massage of the muscles or palpation of the joints or spine during recovery does not cause discomfort.

Ambient temperature
Hot weather does not seem to be necessary to induce collapse, but if the temperature is very warm, collapse is more likely. Affected dogs are less likely to collapse in cold weather or while swimming, but dogs have exhibited collapse while breaking ice retrieving waterfowl in frigid temperatures and dogs have drowned when experiencing EIC-related collapse in the water.

Excitement  
Dogs that exhibit the symptoms of EIC are most likely to have intense, excitable personalities, and it is very apparent that their level of excitement plays a role in inducing the collapse. Dogs with EIC are most likely to collapse when engaging in activities that they find very exciting or stressful. This can include retrieving or chasing live birds, participation in field trials with live birds, training drills with electric collar pressure and quartering for upland game

Type of exercise 
Routine exercise like jogging or hiking is not very likely to induce an episode in dogs with EIC.  Activities with continuous intense exercise, particularly if accompanied by a high level of excitement or anxiety most commonly cause collapse. Activities commonly implicated include pheasant hunting, repetitive "happy retrieves", repetition of difficult retrieves especially where the dog is having trouble finding a bird or is receiving or anticipating electric collar correction, and excitedly running alongside an all-terrain vehicle.

Body temperature
Body temperature is normal at rest in dogs with EIC and is dramatically increased during collapse (often >41.5 C, >107.6F). Temperatures are not different from those seen in unaffected Labrador Retrievers doing the same type and amount of exercise. Dogs lose body heat through panting, so all dogs with these dramatic elevations in body temperature will pant hard in an attempt to cool off.  Although the elevated temperature after exercise may play a role in EIC related collapse (making dogs more dependent on dynamin1 function — see below), and may even contribute to the death of some affected dogs, inability to properly regulate temperature is not the underlying problem in dogs with EIC.

Until October 2008, EIC could only be diagnosed by systematically ruling out all other disorders causing exercise intolerance and collapse and by observing characteristic clinical features, history and laboratory test results in affected dogs. Even today, any Labrador retriever with exercise intolerance should always have a complete veterinary evaluation to rule-out

Even though EIC is the most common reason for exercise/excitement induced collapse in Labrador retrievers that seem otherwise normal and healthy between collapse episodes, there are many other reasons for Labrador retrievers to collapse.

If a Labrador has episodes of collapse or exercise intolerance they should be fully evaluated by a veterinarian for a number of treatable metabolic, cardiac and neurologic disorders including low blood sugar, low blood cortisol, electrolyte abnormalities, heart failure, cardiac arrhythmias, pulmonary hypertension, respiratory disorders, cauda equina syndrome, muscle disorders and epilepsy.

If the dog has collapse episodes typical of EIC that are always associated with strenuous exercise, and the dog is completely normal between episodes of collapse and is determined to be genetically affected (homozygous E/E), then EIC may be the reason for their collapse. If they have other symptoms, have collapse episodes that are not typical for EIC or that occur unassociated with exercise or if they test genetically EIC clear or as an EIC carrier then EIC is not the reason for their collapse — full veterinary evaluation is warranted.

Genetic (DNA) testing can now be easily performed to confirm a suspected diagnosis of EIC.

DNA testing for the genetic mutation causing EIC susceptibility can now be performed. This is a reliable test for the actual mutation (not linkage) so results are definitive and accurate — determining with certainty whether a dog has one copy of the mutation (E/N: carrier), two copies of the mutation (E/E: affected) or no copies of the mutation (N/N: clear).

Instructions for collecting and submitting samples for testing, sample shipping and the necessary forms are available on the website of the Veterinary Diagnostic Laboratory at the University of Minnesota. In addition to testing blood samples, cheek swabs can be submitted by veterinarians from adult dogs or weaned puppies, and litters of newborn puppies can be tested by sending in dewclaws. Frozen stored semen can also be tested from deceased sires. 

Most (>83 per cent) affected Labradors (EE) experience at least one episode of collapse by the time they are 4 years of age.  Most competitive dogs are unable to continue training and competing at a high level. If trigger activities can be avoided, dogs with d-EIC live normal lives. 

A few EE dogs never exhibit collapse, perhaps because they do not engage in the required strenuous activity with extreme excitement as required to produce collapse. DNA testing is the only way to know for certain whether a dog has dEIC. Dogs that are carriers for the dynamin-1 mutation are clinically normal and have no exercise intolerance.

It is important that owners of dogs with EIC be made aware that the dog's exercise should be stopped at the first hint of incoordination or wobbliness as some affected dogs have died during collapse when their owners allowed or encouraged continuing exercise. Not all of the EIC deaths have occurred in dogs rated as severely affected based on their historical number of episodes of collapse or the amount of activity required to induce previous episodes of collapse.

Occasionally we hear about dogs experiencing recurrent episodes of incoordination or collapse with exercise that are not EIC affected – they are either EIC carriers (E/N) or EIC clear (N/N).  In many cases there are abnormal physical findings detected at rest (heart murmurs, muscle atrophy, pain, etc.) helping to distinguish these dogs from dogs with EIC-related collapse. In others the collapse episodes are subtly different from EIC-related collapse. For example, the age of onset may be older, the episodes may be more sudden in onset (not progressive as exercise continues), the episodes may be very brief (1-2 minutes instead of 10 or 15 minutes), the episodes may involve all 4 legs at once (instead of rear legs first), muscle tone may be increased (instead of decreased), mentation may be abnormal (instead of normal), systemic signs may be evident (unlike EIC), or affected dogs may seem painful during an episode (unlike EIC). The episodes of exercise intolerance in these dogs can be attributed to a number of different disorders including joint pain, heart failure, pulmonary hypertension, anemia, heart rhythm disturbances, laryngeal paralysis, lung disease, low blood sugar,  low blood cortisol, cauda equina syndrome, myasthenia gravis, and muscle disease.

It appears that one of the most common disorders causing episodes of exercise intolerance or collapse after exercise that can be confused with EIC in Labrador retrievers is an atypical seizure disorder.

Atypical seizures/paroxysmal dyskinesia
An episodic movement disorder that may be a form of focal motor seizure has been recognized in Labrador Retrievers.  We have been collecting questionnaires and DNA samples from collapsing Labradors for six years now and we believe this is a common disorder in the breed. This disorder has been called atypical epilepsy, paroxysmal dyskinesia or episodic dyskinesia. We believe that most Labrador retrievers presenting with these episodes have idiopathic epilepsy. The episodes in some dogs are most likely to occur upon waking or being startled, but in many dogs episodes seem to be triggered by exercise, excitement or hyperventilation, leading to confusion with EIC. Signs are different, however, from typical EIC episodes. Some dogs simply stagger and look dazed or confused for a few seconds or minutes and then recover, without ever falling over. Others have a two- to five-minute episode (occasionally longer) where they appear anxious and are unable to stand erect and walk but are able to crawl to their desired location. Some dogs seem to have a severe loss of balance during episodes.  Affected dogs maintain consciousness and can obey commands during episodes. Some dogs have a dramatic decrease in their episode frequency when treated with chronic oral anticonvulsant therapy and some affected dogs develop more classical generalized tonic-clonic (loss of consciousness, falling to their side, paddling) seizures later in life.

Heat exhaustion/heat stroke
Before we were able to test for and diagnose EIC, there were many who felt that EIC collapse episodes were simply a manifestation of recurrent heat exhaustion or heat stroke. The collapse episodes we see in dogs with EIC are, however, very different from collapse episodes associated with heat stroke. Heat stroke severe enough to cause collapse in a dog is life-threatening. Recovery, if it does occur, is slow and prolonged (hours to days) even with intensive treatment. Many affected dogs progress to kidney failure and death. Laboratory evaluation reveals a dramatic increase in the muscle enzyme CK. Mentation changes that are severe, progressive and persistent (for hours to days) occur in 80 per cent of dogs collapsed due to heat stroke. Significant blood vessel wall injury leads to blood clots forming within blood vessels, disseminated intravascular coagulation (DIC), low blood platelets and damage to multiple organs. In contrast, dogs with EIC-related collapse show no laboratory abnormalities and they recover quickly - happy and running around within five to 25 minutes. Besides the severity of collapse episodes, the recurrent nature of EIC-related collapse and the fact that collapse can occur even on days with moderate or cool ambient temperatures helps to distinguish EIC from heat-related illness.