Epilepsy and a Normal Life

I love science. Most of all I like learning about the brain. I am interested in both the psychological and neurologic aspects of the brain. Because dogs learn so quickly and adapt to us I am very interested in applying my human neuroscience knowledge to my dogs. I relish seeing their minds work when I ask them to complete a task.

I became very involved in canine neurology, not by my choosing, a few years ago when Darla was diagnosed with a seizure disorder also known as epilepsy.

Epilepsy is a chronic condition and affects 2.2 million people in the U.S.(4) Working in a neurology practice I encountered patients with epilepsy. I understood the basics but epilepsy is not my passion.

I felt very frustrated when Darla had her first seizure—I knew that we were headed down a long and twisting road, not quite sure what could trigger her next event.

Seizures are caused by deregulation of neuronal activity—Just like our heart; the brain has an electrical circuit. When this circuit is disrupted it can become hyperactive causing deregulation of cellular signals and produce a seizure. This deregulation can be secondary in nature meaning that there is something in the brain causing these changes such as a lesion in the brain, irritation from blood (hemorrhage), increased pressure in the head, infectious, toxic, and metabolic causes. Most often we have no idea why a patient is having seizures and they are diagnosed with idiopathic epilepsy or primary epilepsy. The pathophysiologies of canine and human epilepsy are very similar. (2)

I remember the first night Darla had a seizure. She was in the living room lying on the sofa—her normal spot. About 2 AM I was awoken to a loud crash followed by repetitive banging. I jumped out of bed and ran to the noise. I found Darla in-between the sofa and the coffee table having a tonic-clonic or grand-mal seizure.

I am not sure what I felt at that time. I am sure that many other medical providers would agree with the following statement: you don’t feel, you do. I immediately moved the coffee table to keep her head from hitting it and I began to time the event. Her first seizure lasted about 70 seconds. She lost control of her bladder function and created a large amount of foamy saliva. Like most epileptics, Darla was out of it after her seizure. She had no memory of her name and she was very confused—she could barely put one foot in front of the other without falling.

I called the vet and they stated that she did not need to come in immediately as the seizure stopped and as long as her seizure did not last over 2 minutes and her temp remained normal her episode was not an emergency.

In the following days Darla continued to have more seizures—I was terrified that her food, treats, and certain activities were triggering her seizures. I was obsessed with figuring out triggers so I never had to see her suffer from these seizures again.

After Darla continued to have events I knew that she needed an intervention and my vet agreed. I knew that the antiepileptic drugs (AEDs) available to dogs at her time of diagnosis were not nearly as advanced as human drugs and these agents have terrible side effects. I hated to put Darla on one of those agents but I did not have a choice. You see, epilepsy is not just a chronic condition without a cure but it comes with risk of death. (1)  Darla had to receive treatment.

We tried phenobarbital and Darla did not do well with it. She was very lethargic and had some ataxia. I was talking with a training friend when she mentioned a herbal supplement that had been very helpful for other dogs. Fortunately the supplement worked well for Darla. She was able to gradually stop phenobarbital and was very well controlled for about two years on herbs with little to no adverse effects. I was so happy for her.

After having such a good run with herbals Darla deteriorated a few weeks ago. I had been out and came home to a flipped over crate and a post-ictal dog that was acting fruity. She had 4 more seizures over the next 24 hours, some at the vet’s office. While she was at the vet’s office she had one of her worst seizures. They were unable to stop it with Valium and she had to have phenobarbital. The phenobarbital worked to stop her seizures. When Clint picked her up she was so drugged and still post-ictal—she could barely walk.

My vet is really great. She knew that I was not interested in phenobarbital again as a daily treatment and was happy to prescribe us a newer AED. We landed on Keppra. Keppra is more expensive than phenobarbital. We were able to find a coupon that makes it very affordable. It also has to be dosed three times per day, which is hard, but we have a very good dog walker that can come in and give the afternoon dose if we are not home. Even though the dosing is hard to remember and it is an expensive drug we are so happy with how she is doing!

After about one month on Keppra, Darla is back to her fun-loving Sashi-biting self. At first she was a little ataxic but I am not sure it was due to the Keppra. The ataxia could have been from the large dose of Valium and phenobarbital she was given for seizure abortion, this cleared up about three days after she started the Keppra. She did have some loss of appetite at first but after about 2-3 weeks she was back on her food. Otherwise she has not had any issues. She does have to go back to the vet for blood work but so far so good!

I am so thankful that there are more drug options for Epileptic dogs and that because of these great medicines Epileptic dogs can live an exceptionally close to normal lives!

 

 

 

 

 

  1. Devinsky O, Hesdorffer DC, Thurman DJ, Lhatoo S, Richerson G. Sudden unexpected death in epilepsy: epidemiology, mechanisms, and prevention. Lancet Neurol 2016;15:1075–1088.
  2. Pitkänen A, Lukasiuk K. Molecular and cellular basis of epileptogenesis in symptomatic epilepsy. Epilepsy Behav 2009; 14 Suppl 1:16.
  3. Koestner, A. (1988). Neuropathology of canine epilepsy. Problems in veterinary medicine1(4), 516-534.
  4. Epilepsy Statistics. (n.d.). Retrieved May 17, 2017, from http://www.epilepsy.com/learn/epilepsy-statistics

Yes, even Greyhounds need exercise!

We all have certain parts of our day that we look forward to. I look forward to the mornings. I love my first cup of coffee and my walk. Exercise is very important for me. Exercising keeps me upbeat and energetic.

When I adopted Jethro I was told that he would need hardly any exercise and that Greyhounds are lazy. I remember hearing that a few good sprints per week would be plenty for him. This was a foreign idea to me. I had only owned terriers prior to owning Jethro and they required a lot of exercise or they were impossible to live with. But hey, Clint and I wanted a low maintenance dog so maybe my instincts were wrong.

Life with Jethro started off on the wrong foot. Jethro was a creature of habit and the lack of structure in his new environment was overwhelming for him. Prior to adopting Jethro, I had read an article that suggested waiting to start obedience with a retired racer so that they would be more bonded to you when you started. I felt that I should start training his ASAP but wanted to follow the advice of other more experienced Greyhound owners. Needless to say, Jethro became a very frustrated Greyhound that needed a routine and an outlet for his energy.

After a month of struggling with our new situation, I registered Jethro in obedience class. Our local obedience class was filled with small, yappy, fluffy dogs and big barking dogs in need of some manners. Jethro was freaked out. Fortunately, the trainer knew a thing or two about Greyhounds and hooked up us with another couple that adopted a Greyhound. The humans and the dogs hit it off! Jethro and Champ would get to work in a smaller group that was quite. I picked up some training techniques and felt that I could get Jethro where he needed to be. We started practicing at home.

I stopped reading about Greyhounds and started searching for articles on training headstrong independent dogs. Jethro’s life became very structured. We walked every morning and practiced training exercises at night. I realized Jethro and I both needed a routine if our relationship was going to work out. Walking and training Jethro was great! It stimulated our bond and also helped to alleviate some of his anxiety!

I added Darla to the mix and she loved exercise. I would often walk Darla alone to help with her leash manners when she did something good, I would run with her as her reward. She loved this and we still use running as a reward!

When Sashi came home I was not sure what to expect. I heard that Greyhound pups were land-sharks and difficult. However, I found Sashi’s puppyhood very enjoyable, as long as he was exercised. Sashi had an affinity for chewing on high-end leather goods. I learned quickly that a tired pup with nice meaty bone doesn’t eat your leather accessories. Sashi needed a lot of exercised. My nightly routine included making a vodka and tonic, sitting in a lawn chair, and throwing a ball until Sashi was pooped!

Exercise makes us all feel good, even dogs. Exercise recommendation for dogs varies by breed. Generally speaking, dogs need 30 minutes to 2 hours of exercise per day. It’s hard to say that all Greyhounds need the same amount of exercise per day. As dogs physiologically adapt to exercise—At first, the Greyhound may only be able to walk for 20 minutes but gradually adding time is important to achieve a balanced exercise program. While Greyhounds do enjoy lying around they still need exercise. Exercise is important to their physical and mental well-being.

Even if your dog doesn’t have behavioral problems and isn’t overweight there is nothing like smelling where the neighborhood cat has been and the pee of all the dogs that peed on that scrub before yours!

Southeastern Greyhound Adoption (SEGA) hosts an annual Athletes helping Athletes 5K—this year is our 10th anniversary! In addition to the 5K we also have a fun one-mile walk that you can bring your Greyhounds on. There is nothing simpler or sweeter than getting out and walking with your Greyhound. I hope to see all you Metro Atlanta Greyhound lovers at the 5K!   If you are planning to attend the 5K register here and use the code RUN4FUN17. The first 10 people to use the code will get 5$ off their race registration! I look forward to seeing you and your Greyhound at the 5K!

Liver and Thyroid functions.

Today I am going to discuss liver function in greyhounds as well as thyroid function.

Let’s start with the liver.  The liver is an important organ in metabolism of food and drugs.  There are two main blood markers that we check for liver damage:  alanine aminotransferase (ALT) and aspartate aminotransferase (AST).  ALT is found in the liver and elevated levels are directly correlated with liver damage.  AST is found throughout the body in various cells.  AST can be elevated in hepatic injury but also for other reasons not related to the liver.

Greyhounds have elevated ALT without associated liver damage.  I was puzzled by this and could not find any data about why this would occur.   A genetic change is the most reasonable explanation of the greyhounds’ LTF abnormalities.  Again, selective breeding most likely caused this, and unlike the RBC changes that improve the greyhound’s athletic ability, this is just a side effect.

So if the greyhound has elevated ALT, is that why they cannot process drugs as quickly as non-greyhound dogs?  This is not the case.  In the livers of both humans and dogs there are enzymes called cytochrome P450 (CYP), and these are the liver’s metabolizers of drugs.  There are hundreds of these enzymes, all with different numbers.  Most if the information regarding this came from humans and has been used in dogs.  This area of study is booming and these researchers have found differences in this system between dogs and humans as well as between breeds.

Structure of the POR protein. Based on PyMOL rendering of PDB 1amo. Credit: Emw is licensed under CC-BY-SA 3.0

In particular the greyhounds CYP system is atypical from other dogs.  I am sure that you know greyhounds have issues with anesthesia and the anesthesia they receive should be different than other non-greyhound dogs.  This was originally thought to be from the lack of body fat in greyhounds.  This was found to be less likely after a series of studies looked at drug metabolism.  These studies found that if greyhounds were given a CYP inducer like phenobarbital, they could clear anesthesia agents more quickly; conversely, if a CYP inhibitor (chloramphenicol) was given prior to anesthesia, it would take longer for the drug to be cleared.  This points directly to the CYP system as the cause of delayed drug clearance and not the lack of body fat in the hound.

To sum it up, the changes in the liver enzymes seen in greyhounds does not cause the issues with drug metabolism in the greyhound.  However, the CPY system within the greyhound’s liver is unique and creates the changes in drug metabolism.

Now we have a better understanding of the liver function abnormalities seen in greyhounds, let’s talk about the thyroid valves.

There are four common thyroid tests completed when checking for disease in the thyroid.  They are total T4, free T4, T3, and thyroid stimulating hormone (TSH).  TSH is controlled by the pituitary gland in the brain; it controls the thyroid gland’s production of T3 and T4.  Thus, when TSH is elevated it means that there is not enough T4 or T3, and when the TSH is low it means that there is too much T4 or T3.  TSH and T3 play a large role in the diagnosis of hypothyroidism.  T3 is often more important in hyperthyroidism, as there is less of it made in the thyroid and oftentimes takes longer to become abnormal.

Greyhound’s T4 is oftentimes abnormally low; this has been well documented.  It is important to note that current racers or right-off-the-track retired racers have even lower T4 then non-racing greyhounds.

This posed the question about hypothyroidism in these dogs.  There was a study that gave greyhounds with low T4 synthetic thyroid stimulating hormone.  In a mammal with true hypothyroidism this should have elevated the T4, but this did not occur.

This furthered the idea that greyhounds have baseline low thyroid levels and prompted an additional study.  In this study a radioactive tracer was used to evaluate the thyroid function in greyhounds suspected of hypothyroidism.  The uptake of the tracer was within normal limits compared against dogs with normal thyroid function.  This indicated that hypothyroidism is extremely unlikely in greyhounds.

Greyhounds are different from other dogs for various reasons.  These variations in their lab values should be evaluated by someone who has experience with greyhounds.

I hope this series was helpful and you are more informed about why greyhounds’ lab valves are different from non-greyhound dogs.

 

Court, M. H. (2013). Canine cytochrome P450 (CYP) pharmacogenetics. The Veterinary Clinics of North America. Small Animal Practice43(5), 1027–1038. http://doi.org/10.1016/j.cvsm.2013.05.001
Zaldívar-López, S., Marín, L. M., Iazbik, M. C., Westendorf-Stingle, N., Hensley, S., & Couto, C. G. (2011). Clinical pathology of Greyhounds and other sighthounds. Veterinary Clinical Pathology / American Society for Veterinary Clinical Pathology40(4), 10.1111/j.1939–165X.2011.00360.x. http://doi.org/10.1111/j.1939-165X.2011.00360.x

WBCs and platelets in greyhounds

We discussed the differences in greyhound RBCs and non-greyhound RBCs.  There are two other types of blood cells that are different in greyhounds vs. non-greyhound dogs, the White Blood Cell (WBC) and the platelet. 

RBCs, WBCs, and platelets are made in the bone marrow.  After they are mature they are sent into the blood stream.  As discussed previously, the RBC carries oxygen to the tissues.  The WBC’s job is more complex; lets look at it first. 

WBCs are immune cells.  They fight off viral, bacterial, parasitic, and fungal infections.  This is an important job, and there are multiple cells types and they each specialize on a certain intruder. 

I am going to break down WBCs cells lines as simply as possible.  I want this to be easy to understand for everyone!  If there are any questions please comment or email and I will be happy to address this further. 

There are five main types of WBCs.  Some of them are granulated and have a nucleus or control center (RBCs do not have this).  These granulations are particularly important.  The granules are enzymes within the cell that improve cellular function—i.e. they are the marinade on the foreign evader the WBC is going to destroy.  These are the types of WBCs found in the body:

1.     Neutrophils: most numerous WBC.  Nucleated and have granules.  Responsible for ridding the body of bacterial and fungal infections.

2.     Eosinophils: nucleated with granules.  Responsible for ridding the body of parasites.  Assist in allergic reactions.  Help destroy cancer cells. 

3.     Basophils: nucleated with granules.  Basophils control the histamine response in inflammation.

4.     Lymphocytes: Multiple subsets (T and B cells) of the lymphocyte—complex cell with very important functions.  Some subsets have granules others do not.  All have nuclei.  Help the body rid itself of viral and bacterial invaders and also create memory cells so that when the same infection enters the body again, it will be prepared. 

5.     Monocytes: nucleated without granules.  They have longer lives than the other WBCs.  When mature they migrate to the tissues and organs and hang out there to take care of any potential bacterial evaders. 

With all of this complexity it is hard to believe the immune system does not go haywire more often!

Now lets look at the differences in greyhound labs values vs. non-greyhound dogs. Lower WBC counts are often seen in greyhounds.  This has been well defined and is currently not a point of concern, as it is considered a breed trait.  The eosinophil of the greyhound has been widely studied.  Beginning in the 1960s the greyhound was discovered to have a vacuolated eosinophil, meaning that the granules within the cell would not stain for microscopic examination (FYI staining is a method of putting a dye into cells allowing them to be better evaluated by microscope).  This was odd, as non-greyhound dogs’ eosinophils will stain orange with a quick stain method.  The lack of the staining was concerning, as it appeared to be a toxic cell.  The concern for abnormalities prompted large work-ups looking for a source of the inflammation.  Fortunately, these changes were not pathologic.  This prompted more studies.  In 2005, there was a study published in Veterinarian Clinical Pathology.  This study looked a 49 greyhound blood smears and compared them to 200 non-greyhound dog blood smears.  A more advanced staining method was used than in the 1960’s study.  This study showed that structurally and chemically, the greyhound’s eosinophil was the same as the non-greyhound dogs.  This suggests that there were different staining properties in the greyhound eosinophil but overall it was the same cell seen in non-greyhound dogs.  The cell was deemed not pathologic.

In addition to the changes in the WBC there are also changes in the platelet counts of greyhounds.  First things first, what is a platelet? Platelets are tiny blood cells that are made in the bone marrow with RBCs and WBCs.  They are responsible for blood clotting.  

Greyhounds are known to have low platelet levels.  This is considered to be a breed trait as long as the count is not below 100,000/μL.  Again, I ask why is the greyhound’s platelet different from non-greyhound dogs?  Well there are multiple theories about this.  The first came about in 1994 by PS Sullivan.  This theory has been supported multiple times since and focuses on stem cell competition.  Do you remember the RBCs we talked about a few days ago?  Well, Sullivan posited that when the bone marrow begins creating the building blocks of blood, there is a competition between the cells destined to be platelets and the cells destined to be RBCs.  Due to the need for more RBCs in the greyhound, the poor platelets lose this fight—leading to lower platelet counts.  Another theory focuses on the mature RBCs—due to the amount of oxygen molecules on the RBC, there is a mild loss of oxygen overall when the RBCs release the oxygen into the tissues, and this mild hypoxemia causes an increase in the production of RBCs, thus causing a decreased production of platelets—remember these cells are in competition.  Both of these studies show that the competition between the RBC and the platelet either in the blood or the bone marrow is most likely why greyhounds have lower platelet counts. 

Naturally one would think that greyhounds would be “easy bleeders” due to their low platelet counts.  Well, they are “easy bleeders” but it is not due to the lack of platelets.  Actually, the time it takes for a greyhound to create a platelet plug or the “closing time” is very similar to non-greyhound dogs.  This suggests that greyhounds’ platelets are more active than non-greyhound dogs.  These researchers also looked at the risk for bleeding disorders in greyhounds, but this was very rare and not related to their “easy bleeding” tendencies.  However, the clot strength in the greyhound was weaker than non-greyhound dogs—this most likely is the cause of the “easy bleeding” in greyhounds.  

So why would the greyhound be able to clot quickly with a low platelet count but then create a substandard clot? Aging that points back to the high level of RBCs in the blood.  Due to the high RBC mass in the blood, the plasma (fluid in the bloodstream after removal of RBCs, WBCs, and Platelets) has less Fibrinogen (a protein that aids in clotting).  This is the confusing part; there is actually no difference in the fibrinogen levels in greyhounds vs. non-greyhounds.  The mass of the RBCs within the blood is to blame for the pseudo hypofibrinogenemia.  Additionally, it is thought that greyhounds have enhanced fibrinolysis (the ability to break down clots).  This would keep the greyhound from clotting, as they are at risk due to the increased viscosity of blood during exercise. 

Photo Credit: Cindy Frezon

 To sum up the bleeding tendency of the greyhound goes something like this: greyhounds have low platelet numbers but active platelets and these platelets create clots quickly but the clots lack stability due to low levels of fibrinogen due to elevated RBCs in the blood.  Furthermore, is has been theorized that greyhounds have active fibrinolysis and can break up clots quicker than non-greyhound dogs. 

Whew! Now we have looked at the RBCs, WBCs, Platelets, and hemostasis in the greyhound.  It has been great for be to learn more about this.  I now have an understanding of why these levels are different from non-greyhound dogs and I think this adds to the undeniable coolness of the greyhound! The last series on labs will be next week and it will focus on liver and thyroid functions.  Hope you check it out!  

Iazbik MC, Couto CG. Morphologic characterization of specific granules in Greyhound eosinophils. Vet Clin Pathol. 2005; 34:140–143.
Feature image credit: Cindy Frezon
Sullivan PS, Evans HL, McDonald TP. Platelet concentration and hemoglobin function in greyhounds. J Am Vet Med Assoc. 1994; 205:838–841. [PubMed: 7829376]
Zaldívar-López, S., Marín, L. M., Iazbik, M. C., Westendorf-Stingle, N., Hensley, S., & Couto, C. G. (2011). Clinical pathology of Greyhounds and other sighthounds. Veterinary Clinical Pathology / American Society for Veterinary Clinical Pathology40(4), 10.1111/j.1939–165X.2011.00360.x. http://doi.org/10.1111/j.1939-165X.2011.00360.x

What is up with lab values and Greyhounds?

Like I have said previously, I am a nurse and a researcher.  I like to figure out why things do what they do.  When I got Jethro I was amazed by the difference in laboratory (lab) valves in greyhounds and non-greyhound dogs. 

I searched the Internet looking for studies to show why the difference existed.  I recently found a literature review that does a good job with this but it is very science driven and not accessible to most greyhound owners.

Due to the numerous differences in the greyhound and non-greyhound labs, I am going to do a lab series on the blog looking into the different abnormalities. 

Today I am going to dive into the red blood cell values of the greyhound.

First, let’s talk about the red blood cell (RBC) or erythrocyte.  The RCB is the most common cell in the body.  It is disc-like cell that looks like a jelly doughnut with the jelly squeezed out.  RBCs are important because they house hemoglobin (Hgb), which carries oxygen to the body.  Hemoglobin is a protein within the RBC.  The hemoglobin molecule accepts oxygen from the lungs and carries it throughout the body, bringing nutrient rich blood to our organs.  The hematocrit (Hct) is a measurement of the volume of RBCs in the body—this value is needed to get an accurate hemoglobin measurement.  There are two additional RBC values that are different in non-greyhounds and greyhounds.  They are the Mean corpuscular volume (MCV) and the Mean corpuscular hemoglobin (MCH).  The MCV measures the size of the RBC and the MCH measures the color of the cell. 

Adult blood smear by scooterdmu

That is very basic RBC science.  Let’s now talk about the abnormalities in the greyhound’s valves and what they could mean.  Greyhounds have higher RBC counts.  The higher RBC cases an increase in Hgb concentrations and Hct.  These higher values allow for oxygen to reached stressed muscle cells quicker.  Initially selective breeding, training, and racing were deemed the cause of these changes; however, there are additional studies looking at other possible causes.

An argument against training and racing as a cause for these changes was completed looking at Hemoglobin and Hematocrit values in 5-6 month greyhounds and 9-10 month greyhounds.  This study showed that at 5-6 month the greyhound Hbg and Hct were not much different from non-greyhound dogs and much lower than the greyhounds in the 9-10 months group.  They then looked at the 9-10 month group vs. 12-13 month greyhounds. The differences in Hgb and Hct at 9-10 months vs. 12-13 months were statically insignificant, suggesting that at 9-10 months greyhounds have adult lab valves.

Sashi at 6 months by Cindy Frezon

On the other hand, there are studies to suggest that selective breeding is the cause for these changes.  The hemoglobin molecule in the greyhound has a higher affinity for binding to oxygen.  These studies also found unique amino acids mutations on the Hgb to allow for enhanced oxygen-binding capacity. 

You may be asking, how would breeders know this and know which greyhounds to breed?  Most likely the early dogmen breed greyhounds to be hearty, fast, and recovery quickly to hunt again whenever new quarry was seen.  This need for fast recovery influenced breeding practices, meaning that these hounds that were able to recover quickly again had higher RBC counts and more efficient hemoglobin.  These factors are still considered in breeding programs today – talk to any dogman or woman and they will tell you that test-mating or selecting a breeding pair is a time-consuming task with lots of consideration.  

Darla at the Christmas Cup 2015 by Cindy Frezon

Another interesting fact about greyhound RBC valves is the lives of their RBCs.  In non-greyhound dogs, the life of the RBC is around 100 days.  In Greyhounds the life of the RBC is about 50 days.  There are multiple theories about why this is.  Some believe that greyhounds trap their RBCs in their spleen; however, there is no proof to this theory.  Another theory is that the greyhound’s immune system selectively rids its self of older cells, but again this needs to be studied further for more clarity. 

Greyhound’s blood counts also show elevated MCV or large RBCs.  This was thought to be related to elevated reticulocytes (immature RBCs) in the blood but that is not the case. The increased size is breed specific and most likely due to the higher hemoglobin content within the RBC.  This would allow for more oxygen to reach the muscles and allow for continued activity. 

I hope that after this review you have a better understand of the RBC and why it is different in the greyhound.  As I had said before greyhounds are special dogs that do special things.  I think it is fitting that their labs are special too!  Check in later this week for differences in WBCs and Platelets in greyhounds.

 
Feature Photo Credit: Cindy Frezon
Zaldívar-López, S., Marín, L. M., Iazbik, M. C., Westendorf-Stingle, N., Hensley, S., & Couto, C. G. (2011). Clinical pathology of Greyhounds and other sighthounds. Veterinary Clinical Pathology / American Society for Veterinary Clinical Pathology40(4), 10.1111/j.1939–165X.2011.00360.x. http://doi.org/10.1111/j.1939-165X.2011.00360.x