Paroxysmal gluten-sensitive dyskinesia in Border Terriers

Introduction 

Canine epileptoid cramping syndrome (CECS) has been known to Border Terrier breeders and owners since the turn of the century, although the condition is sometimes referred to as “Spike’s disease” after one of the first dogs to be recognized with the disorder (Figure 1). In fact the CECS terminology is a misnomer, as the word “epileptoid” implies an epileptic disorder; recent work has shown that this condition is distinct to epilepsy and that the syndrome is a manifestation of a group of previously unrecognized, but relatively common, conditions referred to as paroxysmal dyskinesias or movement disorders. The more recently coined term paroxysmal gluten sensitive dyskinesia (PGSD) should now be used, as this more accurately describes the condition and its pathophysiology.

What is it?

The term “dyskinesia” is a Greek word literally meaning “bad movement” with the term “paroxysmal” used to depict the intermittent nature of the problem. Paroxysmal dyskinesias or movement disorders are a group of conditions characterized by episodes of abnormal movement in dogs and cats; these events are self-limiting, and there are long periods of normality between the episodes. 

Paroxysmal dyskinesia can be seen in any dog breed. If signs consistent with a paroxysmal dyskinesia are seen then it is classified according to the inciting cause (Figure 2). The vast majority of paroxysmal dyskinesia reported in dogs breeds are referred to as paroxysmal non-kinesigenic dyskinesia. The one exception is a paroxysmal kinesigenic dyskinesia that has been recognized in German Short-Haired Pointers incited by sudden movement 1 12. PGSD is one type of paroxysmal dyskinesia, and it is very specifically associated with the condition presumed to be a manifestation of gluten intolerance in the Border Terrier. No other breed has yet been recognized to have a PGSD. Other breeds exhibiting similar signs should be considered to have a paroxysmal dyskinesia (as opposed to PGSD). Whilst a dyskinesia can occur in any breed of dog, a few breed-specific paroxysmal dyskinesias are recognized, e.g., episodic falling in the Cavalier King Charles Spaniel and paroxysmal dyskinesia associated with Soft Coated Wheaten Terriers 1. These latter two examples are mentioned simply because a causative genetic mutation has been identified which can be used to definitively diagnose this condition in these two breeds.

What does dyskinesia look like?

During an episode of dyskinesia a dog will remain fully alert. This is a key factor to consider, because any loss of consciousness or awareness during an episode would rule out this condition as a differential diagnosis. Affected dogs will exhibit involuntary movements of one or more limbs during the event. These abnormal movements can sometimes be brief and fairly mild, with the dog showing just a little bit of unsteadiness or incoordination of a single limb. However other dogs may have very severe episodes, resulting in collapse and involving the entire body – despite being fully aware – and these can be very distressing to both the dog and the owner. During these extreme episodes very severe muscle contractions may occur. While some mild episodes may be fairly short, the severe episodes can last well over an hour. Once an episode is over, recovery is immediate – a dog will get to its feet and almost instantly revert back to normal, in contrast to a prolonged epileptic seizure in which a period of disorientation is usually observed following the abnormal activity. There is no “aura” before a dyskinesia episode or post-ictal signs following an episode. Dogs are completely normal between episodes and show no problems at all until the next episode occurs. Frequency, severity, and episode length can vary dramatically between dogs but also within individuals. Importantly, paroxysmal dyskinesia is not thought to be life-threatening or to influence life expectancy, with affected dogs often living long, full lives. A video of a typical example of PGSD can be found on line*.

* www.youtube.com/watch?v=hkqrFinzqxE&t=21s.

PGSD shares all the above features, but is unique when compared to other paroxysmal dyskinesias, in that up to 50% of affected Border Terriers may also show signs suggestive of gastrointestinal (GI) disease, either between episodes or during the episode. Signs that may be observed include vomiting, diarrhea, and borborygmi, or there may be non-specific episodes in which a dog may stare vacantly into space, yet remain responsive (Figure 3), licking its lips and appearing to be in pain, with an arched back and tense abdominal muscles 2. It is thought this latter sign may represent a manifestation of esophageal reflux (or “heartburn”), which, as in the human condition, can cause significant discomfort. Other signs occasionally reported in Border Terriers with PGSD are those suggestive of atopy, such as frequent itching of the skin and ears (Figure 4) or frequent licking or chewing at the paws. It is these features that make PGSD unique to other types of paroxysmal dyskinesia. 

When do the signs first appear?

Border Terriers usually start showing signs of PGSD while young, often experiencing their first episode by two years of age. In some dogs the episodes can be triggered by excitement, a sudden burst of energy or something that startles them, but others appear have episodes without any apparent trigger.

What can mimic PGSD?

When managing Border Terriers presenting with paroxysmal episodes it is important to characterize what the episodes most likely represent. PGSD is most commonly mistaken for epileptic seizures by veterinarians and owners alike. However, certain features can be assessed that allow a correct diagnosis of paroxysmal dyskinesia to be achieved 1, as shown in Table 1. 

What happens in PGSD?

As is the case with most paroxysmal dyskinesias, PGSD is believed to result from a dysfunction in the area of the brain known as the basal ganglia. However, much has yet to be learned about how and why paroxysmal dyskinesias occur, and PGSD is no exception.

The majority of paroxysmal dyskinesias are thought to be genetic in nature and this has been confirmed by studies in Cavalier King Charles Spaniels (so-called hypertonicity syndrome 3 4 and Soft Coated Wheaten Terriers 5 in which a genetic mutation has been found (BCAN and PIGN respectively) that can be used as a diagnostic test for the conditions in these breeds. Other breeds known to be affected include Jack Russell Terriers, Labrador Retrievers, Chinooks, Scottish Terriers and Norwich Terriers. This implicates a familial link.

What causes PGSD?

Since the early reports of PGSD, owners and breeders have become aware that affected Border Terriers responded to specific diets. A recent study involving an owner-based questionnaire identified that around 50% of respondents had Border Terriers that improved when fed a hypoallergenic or gluten-free diet 6. Careful analysis of some of these diets suggested that all responder dogs had in fact been on a gluten-free diet.

Research in people has demonstrated that gluten sensitivity is a common cause for many conditions 7. One of the best known gluten disorders in people is celiac disease, whereby the immune system mistakenly produces antibodies against gluten that damage the hair-like villi that line the intestinal tract, leading to malnutrition. Blood tests to detect these antibodies have been developed to help diagnose the condition, and this has identified many people that have only mild symptoms and are often unaware of their condition. Although specificity is excellent, sensitivity is low and so a combination of tests is usually performed to maximize sensitivity.

Gluten is now being blamed for causing bloating, GI pain, headaches and lethargy in many people who do not show an abnormal immune reaction. This syndrome has been dubbed non-celiac gluten sensitivity (NCGS), and although its prevalence is controversial, there have been claims that up to a fifth of people have it 8. A rare neurological condition termed gluten ataxia has also been identified, whereby antibodies to gluten affect cerebellar function, leading to abnormal gait and impaired motor skills, resulting in loss of coordination and significant, progressive disability in some cases 9. In most cases there are no signs of GI disease, although in a small proportion of people diarrhea and stomach cramps may be seen.

Research into PGSD in Border Terriers is as yet limited. However one small study investigated six Border Terriers with suspected PGSD; antibody levels to gluten (anti-gliadin IgG and transglutamise-2 IgA antibodies) were measured by ELISA before starting the dogs on a gluten-free diet, and the serology was repeated after 3, 6 and 9 months on the diet. The affected Border Terriers had much higher concentrations of gluten antibodies before starting the gluten-free diet compared to healthy Border Terriers, but the antibody concentrations decreased after starting the diet and were back to normal levels 9 months later. Furthermore, the dogs stopped having episodes of paroxysmal dyskinesia, although one dog in the study did scavenge horse manure (which is rich in gluten) and continued to have episodes until the owners became aware of this and prevented its consumption. Two other dogs responded well but were inadvertently given treats containing gluten after the study finished, causing a relapse of episodes. However, by returning back to a gluten-free diet these dogs went back into remission 10.

How do I diagnose PGSD?

Videos remain an integral way for the clinician to make a diagnosis. The consulting room is rarely the correct environment to diagnose dogs with such obviously intermittent episodes, as they are inevitably normal by the time they present to the veterinary practice. Therefore it is always advisable to request that the owner captures an episode on video to allow the clinician to scrutinize the recording for signs compatible with paroxysmal dyskinesia. One study noted that many dogs diagnosed with paroxysmal dyskinesia have undergone thorough neurological testing and in each case all results were found to be normal 11. However, standard neurological tests are important to ensure other conditions are not present that may cause life-threatening problems.

If a Border Terrier is presented with signs typical of PGSD, it is appropriate to test for anti-gliadin and transglutamise-2 antibodies, as many laboratories now offer these assays. However, the tests are only reliable if the dog is not receiving a gluten-free diet. If an animal is already on a gluten-free diet, the concentration of gluten antibodies will be artificially decreased and so a negative result may be obtained despite the dog suffering from PGSD. Testing in breeds other than Border Terriers has not been evaluated.

How do I treat PGSD?

It is important to emphasize that PGSD (and indeed any form of paroxysmal dyskinesia) is not life-threatening (Figure 5). Although episodes may be very disturbing to observe, there are no reports of any deaths related to a dyskinesia episode. However, such episodes clearly impinge on a dog’s quality of life and so any treatment that can be offered is worth pursuing. 

The institution of a gluten-free diet is now integral to the treatment regime of PGSD, but only after serological testing has been performed. Gluten is a protein source which is a composite of two amino acid chains (gliadin and glutenin) present in the endosperm of grass-related grains, including wheat, barley and rye. Proteins from maize (corn) and rice are often mislabeled as gluten when in fact they lack gliadin. Going truly gluten-free means excluding the large number of foodstuffs that contain these grains, and will often require excluding anything containing oats, as such grains are often processed using machinery which has previously been used to treat wheat. The author has found Royal Canin Hypoallergenic diet (hydrolysed protein) to be the most effective diet when treating affected dogs 10. Although other diets may also be effective, this product has consistently improved Border Terriers suffering from PGSD and is the author’s preferred diet to trial if a dog is suspected to have PGSD, although it is again emphasized that serum antibody tests should be performed before commencing the diet.

How can I monitor PGSD?

It is recommended that once a positive test for gluten anti-bodies has been obtained and a gluten-free diet is initiated, antibody concentrations should be checked every three months to ensure the values are returning to a normal level. It is also important for the owner to keep a diary of episodes to ensure they are reducing in frequency once the diet has been commenced. If the antibody concentrations are not decreasing and the dog continues to have episodes then it is very important to ensure dietary compliance and check that the dog has not been scavenging or inadvertently receiving other foods.

What is the prognosis for PGSD?

As mentioned above, a dog with paroxysmal dyskinesia or PGSD is a happy dog other than when episodes are seen. Life expectancy is not reduced and therefore the institution of a gluten-free diet – after a diagnosis has been made through serological testing – should result in a good long-term remission from this condition.