video shared with the owner’s permission
Breeders of Norwich Terriers have been long aware of a seizure disorder in the breed. Some feverishly insist on calling it epilepsy, while others cling to the word “cramp”. The first published mention of the condition in the veterinary literature was in 1984 in a letter by R.M. Furber published in the Veterinary Record (UK), entitled “Cramp in Norwich Terriers”. The name “cramp” bore close resemblance to a disorder found in Scottish Terriers.
In referring to the Norwich seizure disorder as either “epilepsy” or “Norwich cramp” breeders have been pronouncing their opinion not so much about the pathology but about the inheritability of the disorder. The “cramp camp” has been implying an environmentally triggered disease, not necessarily inherited, speculated to be metabolic in nature and addressed by diet alongside Vitamin E and Selenium regimen. The “epilepsy camp” has been pouring over pedigrees of seizure prone dogs, mapping clear genetic ties between affected Norwich Terriers and focusing on the apparent genetic component. A nomenclature war has been raging, to the point that some breeders have refused to participate in recent research into the condition in the UK, because the words used to describe the proposed study did not say “epilepsy”. It is a real pity, because science has a way of revealing the truth.
As for the words to use, we might need to learn some new ones. The first scientific paper on Norwich seizure disorder, penned as the result of the aforementioned recent study in England calls it Paroxysmal Dyskinesia. I will add my own preference here to call it Atypical Seizure Disorder, a name used interchangeably with Paroxysmal Dyskinesia when describing the disorder in other breeds.
WHAT WE KNOW THUS FAR
1. The Norwich seizure disorder is not the Scotty cramp
What Norwich Terriers suffer from is not a Norwich version of the “Scotty cramp”. The condition affecting Scottish Terriers is a hereditary neurotransmitter defect: a problem in serotonin metabolism causing its deficiency. The fact that both Scotties and Norwiches remain conscious through an episode is the only similarity. The Scotty disorder, which has a recessive mode of inheritance, can be verified in a diagnostic test.
Pharmacological experiments found decreased levels of serotonin in the central nervous system in affected Scottish Terriers following an episode. When amphetamine or parachlorophenyalanine was administered, the severity of the clinical signs increased. Also, a serotonin receptor blocker methysergide increased the clinical signs in a dose-dependent manner and has been used as a test to diagnose the condition. It is a reliable test, even though the method of using a drug to increase severity of symptoms in order to diagnose the condition is controversial.
2. We have no genetic breakthroughs so far
Immediately after the separation of the Norwich and Norfolk Terrier Club into two separate breed clubs in 2009, the new Norwich Terrier Club of America (NTCA) focused on addressing the seizure disorder in the breed. We teamed up with Dr. Gary Johnson’s lab at University of Missouri collecting samples of affected dogs for their Canine Epilepsy Network (CEN). In spite of several announcements of incremental breakthroughs in mapping epilepsy in other breeds, the Norwich Terrier genome did not yield progress in mapping epilepsy.
Then, the American Kennel Club Canine Health Foundation (CHF) announced a major research project of canine epilepsy co-funded with a number of European institutions and with a very large government funding from European Union. We threw our wholehearted support behind the project, led by Dr. Hannes Lohi at the University of Helsinki in Finland. The NTCA donated generously to the study. We arranged for a collection of Norwich Terrier samples and for sample-sharing between CEN and the European project. Dr. Lohi’s team worked with DNA samples from several breeds alongside those from the Norwich Terrier: Lagotto Romagnolo, Australian Shepherd, Vizsla, and Finnish Spitz, among others, and they found mutation LGI2 responsible for canine epilepsy in Lagotto Romagnolo dogs. So far no correlation has been found in genetic studies comparing any of the suspect regions in other breeds of dogs suffering from epilepsy with the Norwich Terrier genome.
3. A diagnosis of idiopathic epilepsy is a catchall description, not a positive diagnosis
Many Norwich terriers suffering from seizure episodes have been diagnosed by veterinarians and veterinary neurologists as having “idiopathic epilepsy”. Idiopathic means there is no underlying cause, while “epilepsy” is a general term for neurological disorders that are characterized by recurrent seizures.
A diagnosis of idiopathic epilepsy does not answer the question of the causes of the disease, nor its pathology. When we say that the Scotty cramp is not a form of epilepsy we are referring to the fact that Scotty cramp has been proven to be a metabolic defect of serotonin. What we know so far is that Norwich seizures are completely distinct from the “Scotty cramp”, and so the use of the word “cramp” to describe the Norwich seizure condition is fallacious. However, DNA analysis has not yet identified a gene or complex of genes associated with seizures in the Norwich Terrier. Thus, when a Norwich is diagnosed with idiopathic epilepsy, it means that the precise nature of the disorder has not been well described and classified in the veterinary literature, and therefore the dog is diagnosed as having a recurrent seizure disorder (epilepsy) of unknown causes (idiopathic).
1. British study on Paroxysmal Dyskinesia
The first scientific paper on the seizure condition affecting Norwich Terriers was a result of data compilation based on owners’ questionnaires and other records submitted by the owners of affected Norwich Terriers. The owners of Norwich terriers born since January 1, 2000 were invited to complete a questionnaire aimed at identifying affected and unaffected dogs and investigating the clinical characteristics of their seizures. Additionally, pedigrees were studied.
To quote the study results:
‘The questionnaire was returned for 198 Norwich terrier dogs. Of these, 26 (13%) were classified as affected by paroxysmal dyskinesia after revision of the questionnaires and after obtaining videos of the episodes, veterinary medical records, and telephone interviews with the owners. All dogs were neurologically normal between episodes. No significant abnormalities were detected on diagnostic investigations. Mean age at the first episode was 3 years. The episodes were characterized by sustained muscular hypertonicity in the pelvic limbs, lumbar region, and thoracic limbs, impairing posture and locomotion without loss of consciousness. Episode frequency varied both between and within individuals. Stress, anxiety, excitement, and variation in daily routine were recognized as episode triggers in 13 dogs. Episode duration generally was from 2 to 5 minutes (range, from < 2 to 30 minutes). The majority of affected dogs were related.
Conclusions: Paroxysmal dyskinesia segregates in an extended pedigree of Norwich terrier dogs and thus is potentially an inherited disorder in this breed.” [De Risio L., Forman O.P., Mellersh C.S. and Freeman J. (2016), Paroxysmal Dyskinesia in Norwich Terrier Dogs. Movmnt Disords Clncl Practice, 3:573-579. Doi:10.1002/mdc3.12334.]
For the first time ever, this recently published study by Dr. Luisa De Risio and her coinvestigators offers us a classification of the disorder by calling it Paroxysmal Dyskinesia and confirms a genetic component suspicion.
2. Labrador study at University of Minnesota
A study at Canine Genetics Lab at University of Minnesota might be helpful to us in understanding what Paroxysmal Dyskinesia is. After 20 years of compiling medical records for Labrador Retrievers and Retriever/ Poodle crosses diagnosed with idiopathic epilepsy, the researchers have recognized that a significant proportion of Labrador retrievers present with atypical events where the dogs remain conscious and the seizure is focal movement rather than convulsions. They labelled them Paroxysmal Dyskinesia or Atypical Seizure Disorder.
“Some Labradors with these atypical seizures simply stagger and look dazed or confused for a few seconds or minutes and then recover, without ever falling over. Others have a 2 to 5 minute episode (occasionally longer) where they appear anxious and are unable to stand erect and walk but they will attempt to crawl to their desired location. Some dogs will experience either uncontrollable trembling or increased muscle tone during an episode and a few simply develop a head tremor or trembling while they remain abnormally quiet and recumbent. Affected dogs maintain consciousness and appear to be visual, able to recognize their owners […] Affected dogs are normal between these episodes which occur suddenly, without warning. Systemic evaluation for metabolic, neoplastic and infectious causes of seizures is negative and repeated toxin exposure is unlikely. Related dogs may be similarly affected.”
Where it gets really interesting is the data on the efficacy of various treatment protocols and the progression of the disease over time. Those two factors favor the nomenclature of Atypical Seizure Disorder.
“In support of this Labrador disorder being a seizure disorder, we have determined that many affected dogs will have a dramatic decrease in their episode frequency when treated with chronic oral anticonvulsant therapy and some affected dogs also develop more classical generalized tonic-clonic seizures later in life.” [study’s webpage]
3. Reports on successful treatment protocols and seizure presentation in a voluntary data submission by owners of affected Norwich Terriers in America
After publication of the British paper, which was based on owner reports, I embarked on a similar, much smaller scale project of my own. I asked owners of affected Norwich Terriers in America to voluntarily submit a list of treatments and their efficacy as perceived by the dog’s owner. I made my request on two online yahoo groups for Norwich owners with combined membership of 972 dog owners. I received 26 responses from the owners of affected dogs, three of them being from owners of dogs known to be Norwich Terrier mixes. Some respondents answered my question about treatment protocol used, while others supplemented that information with extensive descriptions of the seizure history, videos and pedigrees.
The affected dogs whose pedigrees were sent to me (unsolicited) all showed common ancestry. The most common type of seizure reported was a movement seizure with the dog remaining conscious, however there were 4 dogs reporting seizures that involved the whole body, eye rolling, bowel movement and loss of consciousness. One of those dogs was a Norwich mix with a Cairn Terrier confirmed through a Wisdom Panel test, a DNA test showing breed genome.
The treatments varied from diet change to anticonvulsants. Diet change involved either refraining from certain kind of protein, or protein rotation between single-protein foods. 14 dogs responded to Vitamin E and Selenium supplements. The regime varied greatly from the lowest dose being Vitamin E, 50 units and Selenium, 12.5mcg every 4 days to a protocol of Vitamin E 400 units twice daily and Selenium 50 mg twice daily. All owners noticed a reduction in seizure frequency and sometimes in severity as well. All owners used a limited protein diet or protein rotation alongside the vitamin/ mineral protocol. One owner was giving her dog a high dose of Vitamin E only and noticed a reduction in episodes before learning of Selenium being a part of the protocol as well.
Treatments with anticonvulsant drugs included Phenobarbital and Bromide, Levetiracetam, Valproic acid and Zonisamide. The drug reported by the dogs’ owners as having most notable decrease in seizure severity and frequency was Zonisamide. Dogs with a movement seizure (twitching, stiffening, wobbly walk or paddling while the dog remains conscious) responded well to anticonvulsants, as did the dogs with a more severe presentation of seizures, including consciousness loss. This is very important information because it confirms epilepsy as an underlying pathology.
Therefore, we might be dealing with two seizure disorders, one being convulsive form of epilepsy with tonic-clonic seizures and the other one Atypical Seizure Disorder (Paroxysmal Dyskinesia). However, it is more probable that we are observing varying degrees of dogs being affected with the same Atypical Seizure Disorder, just as it is found in the Labrador Retriever, where some dogs with Atypical Seizure Disorder develop tonic-clonic seizures.
The time has come to put one thing to bed: inheritability. The disorder is genetic. I hope that we can move towards organizing a study of Atypical Seizure Disorder, shift our attention away from hoping that the idiopathic epilepsy studies will give us a DNA test, and concentrate on further study of the atypical characteristics of the seizure disorder in Norwich Terriers that puts it in the paroxysmal dyskinesia category. And finally, let’s stop breeding dogs with any concentration of affected ancestors in their pedigrees, or a cluster of ancestors that have been proven to carry the disease (as they may produce affected progeny).
Note: If you have a video illustrating a seizure episode in a Norwich Terrier and would like to share it in my blog I would be very grateful. Visual representation of various seizures would be most illustrative.