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Epileptoid cramping syndrome
Synonym(s): PGSD, Paroxysmal gluten-sensitive dyskinesia, Paroxysmal dyskinesia, CECS, Spike’s disease
Introduction
- First recognized in 1997 by German veterinarian Diana Plange after a number of dogs bred by a single breeder were affected. Recognized in 1999 in the US.
- Definition: the term Canine epileptoid cramping syndrome (CECS) is actually a misnomer as the condition has no association with epilepsy. It is a form of paroxysmal dyskinesia (PD).
- The term ‘dyskinesia’ is a Greek word literally meaning ‘bad movement’ with paroxysmal depicting the intermittent nature of the problem.
- The term paroxysmal gluten sensitive dyskinesia is now preferred (PGSD).
- Cause: PGSD is thought to be due to a gluten sensitivity.
- Signs: episodic involuntary movements including:
- Ballismus - abrupt contraction of limb muscles causing a flailing movement of the limb, this is often unilateral, as in hemiballismus).
- Dystonia - sustained involuntary contraction of a group of muscles producing abnormal postures).
- Chorea - abrupt, non-sustained contraction of different groups of muscles in the same patient).
- Athetosis - prolonged contraction of trunk muscles causing a bending or writhing motion, this often accompanies chorea, thus described as choreathetosis).
- These signs can be seen in any breed of any dog but PGSD is unique in that it may be associated with additional signs suggestive of gastrointestinal disease such as intermittent vomiting, diarrhea, borborygmi (ie loud gut noises) and abdominal cramping.
- Some affected dogs will also show frequent signs suggestive of atopy such as scratching, chewing and licking at the skin.
- Diagnosis: is by inspection (ie observing a typical episode recorded by the owner) with clinical history, potential gastrointestinal and skin involvement and episode phenomenology being fundamental to this diagnosis. Serological testing for anti-gliadin and transglumainase-2 antibodies can confirm a diagnosis.
- Treatment: a gluten free diet has been shown to be successful with dogs going into complete remission for both the neurological signs and the signs suggestive of gastrointestinal and dermatological problems.
- Prognosis: prognosis is usually excellent with dogs responding very well to the diet.
- Episodes are not life-threatening and do not appear to progress.
Presenting signs
- During an episode of dyskinesia a dog will remain fully alert Canine epileptoid cramping syndrome:
- This is a key factor to consider because any loss of consciousness or awareness would rule-out this condition.
- Episodic involuntary movements of one or more limbs:
- 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 or may be severe resulting in collapse and involving the entire body.
- Severe muscle contractions may occur.
- Episodes may be short (seconds to minutes) or long (lasting well over 1 hour).
- There is no “aura” before the episode or post-ictal signs following the episode.
- Dogs are completely normal in 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.
- Up to 50% of Border Terriers with PGSD may also show gastrointestinal signs in between or during the episode:
- Signs that may be observed include vomiting, diarrhea or non-specific episodes in which a dog may stare vacantly, licking their lips and appearing painful with an arched back and tense abdominal muscles. It is thought the latter sign may represent a manifestation of esophageal reflux (or ‘heartburn’), which can cause significant discomfort.
- Other signs occasionally reported include frequent itching of the skin and ears or frequent licking or chewing at the paws. It is these features that make PGSD unique to other types of paroxysmal dyskinesia.
Geographic incidence
- More common in Europe than in US.
Age predisposition
- 6 weeks up to 7 years old (but can be older).
Breed/Species predisposition
- Border terriers Border Terrier.
Pathogenesis
Etiology
- PGSD is considered a secondary PD in the sense that it is triggered and perpetuated by dietary gluten.
- PGSD is similar to a paroxysmal non-kinesigenic dyskinesia (PNKD) in people.
- Pathogenesis of paroxysmal dyskinesias (PD) is not well defined with 2 main theories:
- A manifestation of transient dysfunction of the basal nuclei.
- Single photon emission computed tomography studies demonstrate hyperactivity within the basal ganglia during episodes of PD.
- People with PD may have evidence of lesions affecting the basal ganglia in secondary PD.
- People with PD have diminished ability to store and synthesize dopamine leading to chronic up-regulation in the concentration and affinity of postsynaptic dopamine receptors.
- One hypothesis suggests a sudden excessive release of dopamine can be stimulated by alcohol and coffee resulting in episodes of PD.
- PD is an epileptic disorder.
- Early reports suggested PD was a ‘reflex movement-induced seizure’ due to the association of episodes with sudden movement or startle.
- A single case report in a person demonstrated that episodes of PD disappeared on excision of a cortical scar.
- Pathophysiological mechanisms involve ion channels, in a very similar manner to those under-pinning epileptic seizures.
- Seizures and PD may often occur in the same patient suggesting a similar pathophysiology creating two distinct clinical syndromes.
- Several paroxysmal neurological disorders that are not of epileptic origin (eg episodic ataxia type 1 and 2, familial hemiplegic migraine) have been associated with different ion channel gene mutations, and these same disorders have significant clinical overlap in presentation and treatment when compared to PD.
- Therefore the co-occurrence of epilepsy and PD in some families suggests that a common genetically determined pathophysiological abnormality of ion channel function is variably expressed in the CNS.
- Some people with PDs have mutations in ion channels (e.g. KCNMA1 and SLC2A1).
- A mutation of an ion channel could cause abnormal excitability in the cerebral cortex and basal nuclei under different circumstances, eg an age-dependent expression of different subunits of multi-subunit ion channels may be observed.
- However, recently the finding that PD may be associated with a number of non-ion channel mutations (eg PRRT2 and MR-1), presumably resulting in abnormal proteins that do not seem to mediate channel functions, counters this theory and suggests the possibility of multiple mechanisms contributing to PD.
Predisposing factors
General- Sudden movement.
- Stress, excitement.
- Dietary gluten.
Pathophysiology
- PGSD is believed to be a manifestation of a gluten sensitivity with multi-system manifestations possible (eg signs indicative of dermatological or gastrointestinal disease).
- Research in people has demonstrated that gluten sensitivity is a common cause for many conditions.
- One of the best known gluten disorders in people is celiac disease (CD).
- CD is caused by the immune system mistakenly producing antibodies against gluten that damage the hair-like villi that line the gut, leading to malnutrition.
- Serological testing can be performed to look for these antibodies to help diagnose the condition and this has helped diagnose many people that have only mild symptoms and so are often unaware of their condition.
- Although specificity is excellent, sensitivity is low and so combinations of tests are usually performed to maximize sensitivity.
- Gluten is now being blamed for causing bloating, gut pain, headaches and lethargy in many people in whom there is no immune reaction.
- This syndrome in people has been dubbed non-celiac gluten sensitivity (NCGS), and there have been claims that up to a fifth of people have it.
- A neurological condition in people called gluten ataxia has shown how gluten can affect the brain without causing signs of gut disease, although in a small proportion diarrhea and stomach cramps may still be seen.
- Patients with gluten ataxia have macroscopic cerebellar atrophy visible on MRI with diffuse infiltration of T lymphocytes within the cerebellar white matter and perivascular cuffing with inflammatory cells.
- In Border terriers with PGSD, antibodies to gluten (gliadin and transglutaminase-2) have been found to be increased compared to control dogs.
- These antibody titers reduce following the institution of a gluten free diet.
Timecourse
- Dogs may present as young as 3 months old up to 13 years of age.
- Episode frequency and duration is highly variable.
Diagnosis
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Treatment
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Prevention
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Outcomes
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Further Reading
Publications
Refereed papers
- Recent references from PubMed and VetMedResource.
- Lowrie M, Hadjivassiliou M, Sanders D S, Garden O A (2016) A presumptive case of gluten sensitivity in a border terrier: a multisystem disorder? Vet Rec 179 (22), 573 PubMed.
- Lowrie M, Garden O A, Hadjivassiliou M, Harvey R J, Sanders D S, Powell R, Garosi L (2015) The clinical and serological effect of a gluten-free diet in Border terriers with epileptoid cramping syndrome. JVIM 29, 1564-1568 PubMed.
- Black V, Garosi L, Lowrie M, Harvey R J, Gale J (2014) Phenotypic characterisation of canine epileptoid cramping syndrome in the Border terrier. JSAP 55, 102-107 PubMed.