Polymyositis in the Nederlandse Kooikerhondje

By Yvet Opmeer, (DVM and PhD student), and Paul Mandigers

 

One of the many ongoing research projects in the neurology group focuses on the Kooikerhondje. The Nederlandse Kooikerhondje is traditionally a working dog for the duck hunt. When the endenkoois started to disappear at the beginning of the 20^thcentury, the breed was endangered to go extinct. After the second world war, a lot was done to safe the breed. A small genetic foundation of 40 ancestors was formed. Since then, the population has grown a lot. In the meantime, more than 28.000 Kooikerhondjes were bred of whom currently about 7000 are alive.

 

Today, the Kooikerhondje is an internationally recognized breed with registrations in Europe, Japan and the United States of America. The Kooikerhondje has, like other breeds, many health issues. For two breed specific diseases, the responsible mutation was found (von Willebrand disease/vWD and the hereditary necrotizing myelopathy/ENM). We are currently working at full speed to research and better understand polymyositis since this illness is limiting the breed quite a bit.

 

The most distinguishing symptoms of this illness are movement and swallowing problems. Dogs with movement problems suffer from a muscle weakness and have a staggered gait. Kooikers with eating problems often drool and have issues swallowing. A combination of both presentations is possible. The diagnosis is made by a combination of symptoms, blood tests, electromyography (EMG) and a muscle biopsy. Usually, the CK (creatinine kinase level) is elevated.

 

A muscle biopsy is necessary for the diagnosis. Additional functional tests can help in finding the best options for management, prognosis and phenotyping. We find two forms of polymyositis in the Kooiker: a granulomatous myositis and a more lympho-histiocytic myositis.

 

The biggest focus of our research is, of course, the identification of the underlying genotype (the mutation). With help of a genome-wide association study (GWAS) and the complete genome sequencing (WGS), we have found a mutation. HOWEVER, not all homozygous (having two identical alleles of the particular gene) Kooiker get sick, and on the contrary, some heterozygous (having two different alleles of the particular gene) animals get sick as well. We hope that we can improve the phenotyping with a better pathological description and immunotyping in order to understand which Kooikers get sick and which don’t. The goal is, of course, to eliminate the disease in the population.

 

Our team consists of Dr. Peter Leegwater, Dr. Hille Fieten (genetics), Prof. Femke Broere (immunology), Prof. Kaspar Matiasek (neuro pathology), Dr. Paul Mandigers (neurology and project manager), Yvet Opmeer (DVM and PhD student) as well as breeder and breed clubs. As you can see, the research is in full speed. If you find in your practice a Kooikerhondje with these clinical symptoms or if you are treating a Kooikerhondje with the diagnosis of Myositis/Polymyositis, please do not hesitate and contact us:

Yvet Opmeer (y.opmeer@uu.nl) or Paul Mandigers (p.j.j.mandigers@uu.nl). With your help, we will be able to extend the research and hopefully, polymyositis will soon be a disease of the past.       

                                                                                                                                               

Translation of the German translation (by Claudia Jurasek) by Susanne Martin, MD

Our Journey with Polymyositis

By Kristin Mersinger

In November 2009, the sweetest little Kooiker, Bristow, registered name Rosewood’s Cato, came in to the world.  He was instantly a part of the family. Bristow’s quirky spirit and loving disposition imprinted on everyone he met. They commented on how beautiful his earrings were and how well behaved he was.

Everyone referred to Bristow as my shadow. Where I went, he was sure to follow. We did everything together – hiking, swimming, playing in the snow. Had I known the fate of his future I would have done more with him.

In April 2018, we had noticed Bristow’s breathing had changed. It appeared labored, pushing more from his diaphragm.  He also seemed to be having trouble making our normal walking distance without taking breaks. We took a trip to the vet where they took chest x-rays and did blood work.  The diagnosis was haziness in his chest, so possible lung infection. All of the blood work came back great except for his CPK levels – those were slightly elevated, but not enough for the vet to see a cause for concern.  We put him on antibiotics for 2 weeks. About 1 week later, Bristow was unable to make it out of the front yard. I took him to the ER where they did additional x-rays and blood work.  Everything came back the same – haziness in chest and CPK levels slightly elevated. Both the vet and the Critical Care doctor stated the CPK levels could be elevated due to his physical state at the time the blood was withdrawn. We continued with the antibiotics and were referred to an Internal Medicine specialist because of the labored breathing.

In May 2018, we made our way in to see the Internal Medicine specialist. Upon arrival, Bristow’s heart rate elevated to around 220. He was immediately admitted in to the ER. They were able to get him to relax and eventually put him on oxygen. All the vets, doctors, specialists were in agreement that something was wrong with Bristow, we just didn’t know what. Multiple tests (CT scans, radiographs, ultrasounds, etc) were done and all of which concluded “unremarkable”.  The day Bristow was to be brought home from the hospital, one of the Critical Care doctors showed a few specialists a video of Bristow walking. They decided to test and treat for Myasthenia Gravis – a disease that causes weakness and rapid fatigue of muscles under voluntary control.  Treatment was Mestinon and Prednisone.  A few days passed and Bristow was walking and playing again. He wasn’t back to 100% but we were so happy that he could walk down the street.  About 2 weeks later, we received the test results – negative. However, we continued with the treatment because of the positive results. The Critical Care doctor then referred us to a neurologist.

In August 2018, we met with the neurologist. He was not convinced (and I agreed) that he had Myasthenia Gravis for two reasons: 1.) Bristow did not have any issues with his esophagus and 2.) the elevated CPK levels. The neurologist believed it was Polymyositis and mentioned a correlation between the disease and elevated CPK levels. However, he wasn’t ready to do further testing because he wasn’t familiar enough with the Kooikerhondjes and Bristow wasn’t showing symptoms (aside from the labored breathing).  We decided to run his bloodwork one more time – if his CPK levels were elevated, he would order an Electromyography (which is an electro diagnostic medicine technique for evaluating and recording the electrical activity produced by skeletal muscles).  The results – normal CPK levels. We decided to take him off the Mestinon but kept him on the Prednisone.

At this point, I’m sure you can imagine how frustrating this process was for us and for poor Bristow. He was such the brave boy. Researching this disease became a full-time job for me. The vets and specialists (along with myself) were so unfamiliar with the breed, we didn’t know where to begin.  One Critical Care doctor’s heart was struck by Bristow and she stood by us until the end. She researched with me, sat with me, was just there to support me.  Any disease I could find with similar symptoms, I would shoot off to her and she would talk me through why it might or might not be that disease.

In September 2018, I noticed an odd change in the way Bristow was drinking and eating. Something seemed off with his tongue. He was also salivating significantly.  We had a follow up appointment with the neurologist, and he noticed his tongue immediately. He mentioned seeing this happen with Vizsla’s and Corgi’s – he called it tongue atrophy. We changed up medications and increased dosages. He was on a high dose of two different types of an immunosuppressant, antibiotics and pain medication. This is where things went downhill quickly. 

A little note about Bristow: he was a very stubborn pup. If he couldn’t do something, he lost interest.  Food was as high of reward as we could get. He would walk on water for cheese, popcorn, bananas. It was difficult for me to figure out what he was able and willing to eat as he could no longer chew food. We placed a piece of cheese in front of him and he turned away from it.  My heart broke with that simple gesture. 

So, we decided to do the Electromyography. The neurologist confirmed the readings of Polymyositis, but the only way to get a full diagnosis was to do the biopsy. And so, we did.  I don’t regret doing the biopsy, but I wish I would have done it in May when Bristow was so much stronger.  The results of the biopsy – Polymyositis. The neurologist was saddened by Bristow’s decline, but wasn’t ready to give up on him.  He gave us a high calorie food to feed with a syringe. Which neither Bristow nor myself were thrilled about. A couple of days after, Bristow finally stopped walking. I carried him from his bed to the yard and back again. The spark was gone from his eyes. It was clear that he was done fighting.  My husband said something very powerful that convinced me it was time to say goodbye.  He reached down, scratched his head and said, “I’m going to miss you, buddy. I’ve been missing you for a while now.”  It was time to let go of my shadow.

I encourage you take notice of the little differences in your pup. Don’t be afraid to ask your breeder questions. Polymyositis is hereditary so learn about your pup’s pedigree.  The more we understand this disease, the faster it can be treated.

Please feel free to contact me or Susanne Martin with any questions

Kristin Mersinger (kfouch9@gmail.com)

 

Polymyositis in Het Nederlandse Kooikerhondje

Yvet Opmeer
BVM (PhD student)

and

Dr. Paul J.J. Mandigers
DVM, PhD, DipECVN, DipRNVA, DipEBVS.
Clinical Associate Professor in Neurology
Department of Clinical Sciences of Companion Animals
Faculty of Veterinary Medicine

Utrecht University
Yalelaan 108, 3584 CM Utrecht, The Netherlands

p.j.j.mandigers@uu.nl

Polymyositis in the Kooikerhondje appears to present in two forms that can either present themselves separately or combined.

The first type is marked by abnormal locomotion and locomotion problems due to general weakness, muscle weakness or stiffness. Most dogs presented with a stiff gait although the exact presentation varies based on which muscle groups are affected. The second type is marked by drinking, eating and swallowing problems. Both types may be present in the same dog. Other clinical signs are lethargy, weight loss, dyspnoea, general weakness, and/or exercise intolerance. Most of the symptoms present between one year and two years of age and there is no apparent predilection for age. Male dogs might be more likely to suffer from the disease than female dogs however.

Diagnosis is made based on the clinical symptoms, blood examination (elevated CPK), an electromyogram and histopathology. The latter is of the utmost importance.

As this disease is most likely immune mediated the basis of the treatment consists of corticosteroids in combination with oral supplements. The response to this treatment varies.

Currently we are investigating this disease (Paul Mandigers: p.j.j.mandigers@uu.nl). As it is most likely hereditary we seek DNA samples of affected Kooikerhondjes. As written above the disease has to be confirmed with histopathology.

How can we help each other?

1. If you have a Kooikerdog under treatment with clinical signs that may fit a polymyositis please notify us. We would like to receive a copy of the patient record including blood test results and of the pedigree.

2. If the CK (or CPK) level is clearly elevated it is most likely a polymyositis case. The next step is to make an EMG (electromyogram) and/or sample muscle tissue. We are happy to get them examined for you. Ideally, we would like to receive a small sample (1 cm by 1 cm by 0.5 cm) of the triceps muscle and of the femoral biceps. Please put the two samples in a 4 to 10% buffered formalin container. You can send it to: Dr. P. Mandigers, University Clinic Faculty of Veterinary Medicine, Yalelaan 108, 3584 CM Utrecht (00 31 30 253 9411).

3. If the CK level is not clearly elevated please consider testing for myasthenia gravis as this is a disorder that occurs in this breed as well.

4. In all cases: if possible, make a video of the moving dog or when the dog is eating/swallowing. Videos can be sent in any format using www.wetransfer.com to p.j.j.mandigers@uu.nl

5. In all cases we would like to get a DNA sample. We need 4 ml of EDTA blood. Please send it together with a copy of the pedigree to: Dr. P. Mandigers, University Clinic Faculty of Veterinary Medicine, Yalelaan 108, 3584 CM Utrecht (00 31 30 253 9411)

Based on the diagnosis we can advise you or your veterinarian on the treatment of your dog.

Best wishes

Yvet Opmeer and Paul Mandigers

 

Please check out this website link from the institute of canine biology.

In the Kooikerhondje, a breeder or breed enthusiast should calculate the coefficient of inbreeding going back to 1990 as this seems to capture the important population to look at in our breed.