ROTTWEILERUpdate - IDIOPATHIC EPILEPSY Studies Focus on Etiology & More Effective Treatments - AKC Canine Health Foundation
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
ROTTWEILER Update
®
®
A PURINA PRO PLAN PUBLICATION DEDICATED TO ROTTWEILER ENTHUSIASTS VOLUME 20 | SPRING 2022
IDIOPATHIC EPILEPSY
Studies Focus on Etiology & More Effective Treatments
SPRING 2022
IDIOPATHIC EPILEPSY RESEARCH
MAY ADVANCE TREATMENT FOR AFFECTED ROTTWEILERS
The perplexing nature of idiopathic though nothing had happened,”
epilepsy can be as challenging for says Burke, describing her first
owners to deal with as having an seizure experience after 35 years’
affected dog. The toll from seizures sharing her life with Rottweilers.
that occur for no apparent reason When Dice had a second seizure
affects owners and dogs. Sadly, hours later, worse than the first
some dogs never respond to anti- one, it put him into a cluster seizure
seizure drugs. category, having had more than
Rottweiler owner Raquel Burke one seizure within 24 hours. “This
of South Plainfield, New Jersey, was seizure lasted a bit longer than the
dumbstruck when her 2-year-old male first one, and Dice lost control of his
“Dice” had a seizure in May 2021. The bladder,” Burke says. “What we thought
minute-long episode took down the was a one-time freak occurrence
90-pound dog. He fell over, his stiff became terribly concerning.”
“In the beginning, I wanted body convulsing as foamy saliva An emergency visit to the local
to put a bubble around Dice, oozed from his mouth. veterinary specialty clinic involved
“As he came to, Dice was a bit a thorough examination by a veterinary
but now I want him to enjoy aggressive and disoriented for about neurologist who would not release
20 seconds. After that, it was as Dice to go home until he was seizure-
life and to keep doing the
PHOTO: CAM MORLEY
things he loves.”
Rottweiler owner Raquel Burke of
South Plainfield, New Jersey
“Dice,” a 2-year-old male Rottweiler, had his first seizure last May. Antiseizure drugs
are helping to manage his idiopathic epilepsy.
2
ROTTWEILER Update
SWEDISH EPIDEMIOLOGICAL STUDIES FIND EPILEPSY IS COMMON IN ROTTWEILERS
As in the U.S., the Rottweiler is a popular breed in seemed to increase in the breed over the last decades,”
Sweden. Although epilepsy has not been studied Dr. Heske says. “Although epilepsy appeared to be
extensively in Rottweilers, the most revealing epide- common in the breed, there was little published
miological information about disease incidence and research describing the disease in Rottweilers.”
mortality has come from Sweden. Thus, Dr. Heske led a follow-up study gathering
Veterinary epidemiologist Linda Heske, PhD, of information from a questionnaire sent to owners
the Norwegian University of Life Sciences, was the of Rottweilers diagnosed with epilepsy that were
lead investigator of a study published in 2014 in The registered in the Swedish or Norwegian kennel clubs
Veterinary Journal that ranked Rottweilers seventh between 2007 and 2013. The purpose was to learn
among 35 breeds with the most dog-years-at-risk about the clinical characteristics of the disease in
(DYAR) receiving veterinary care for epilepsy. DYAR the breed. The findings were published in 2015 in the
represents the time period from when a dog is first Swedish journal Acta Veterinaria Scandinavica.
insured, typically at 8 weeks of age, until exiting “Clinical Characteristics of Epilepsy of Unknown
the insurance database due to death, becoming an Origin in the Rottweiler Breed” shared insights
epileptic case or the end of the study. learned from 37 epileptic dog cases, 23 females
The report tapped into the Swedish animal insur- and 14 males.
ance database to learn about the incidence and The median age of the onset of seizures was 36
mortality rates of epilepsy in a large population of months, though seizure onset ranged from 8 to 84
insured dogs representing 197 breeds. Dr. Heske, a months. Twenty-four of 37 dogs were on antiseizure
doctoral student at the time of the research, evaluated drugs, yet owners reported limited improvement in
veterinary records from 1995 to 2006 that accounted seizure frequency. All the affected dogs had relatives
for more than 2 million DYAR data. with epilepsy. Seven dogs were neutered after the
The findings showed that Rottweilers had an epilepsy onset of seizures, but none experienced reduced
incidence rate of 24.3 cases per 10,000 DYAR com- seizure frequency or intensity.
pared to an average of 18 cases per 10,000 DYAR for “The majority of cases were idiopathic epilepsy in
all dogs. The breed’s mortality rate of 21.5 deaths per which no morphological cause can be found,” Dr. Heske
10,000 DYAR placed Rottweilers as the fourth most says. “Over half of Rottweilers with epilepsy were
common breed to succumb to the disease. reported to have cluster seizures, or two or more in
“The higher-than-average incidence and mortality a 24-hour period, and their responses to antiseizure
rates of epilepsy for Rottweilers mirrors the obser- treatment were variable. This retrospective study
vations of veterinary practitioners and Rottweiler provides the first detailed characterization of epilepsy
breeders and owners in Sweden that epilepsy has of unknown origin in the Rottweiler breed.”
free for 24 hours. He was started on to an average of 18 cases per 10,000 prompted his veterinarians to make
the antiseizure drug phenobarbital, DYAR for all dogs. The study also dosage adjustments based on
which worked magic, giving Dice found that with a mortality rate Dice’s bloodwork.
six months without seizures. of 21.5 deaths per 10,000 DYAR, “Treating idiopathic epilepsy is
Burke recalls hearing someone say Rottweilers rank as the fourth most basically trial and error since it is
early in Dice’s treatment journey common breed to die from epilepsy. not known what causes the seizures,”
that Rottweilers are predisposed to (See “Swedish Epidemiological Studies Burke says. “In the beginning, I want-
idiopathic epilepsy, something she Find Epilepsy Is Common in Rott- ed to put a bubble around Dice, but
had never heard. weilers” above.) now I want him to enjoy life and to
Although breed prevalence has Dice had a mild breakthrough keep doing the things he loves. It’s
not been studied extensively in the seizure last October even with his easy to feel like it’s your fault your
U.S., an epidemiological study in regular doses of phenobarbital, dog has seizures, but you shouldn’t
Sweden found that Rottweilers followed by another one a couple be too hard on yourself.”
have an epilepsy incidence rate of of weeks later in early November. Lisa Wingerter of Evansville, Indiana,
24.3 cases per 10,000 dog-years- A second antiseizure drug, leveti- blamed herself when her first Rott-
at-risk (DYAR) based on insurance racetam (Keppra®), was prescribed. weiler, “Pagan,” a female, had a seizure
data from 1995 to 2006 compared Since then, two more mild seizures in 1992 at age 4 following spay sur-
3
SPRING 2022
PHOTO: LISA CLARE
Purina and the AKC
Canine Health Foundation
“Pagan,” a female Rottweiler, was treated for idiopathic epilepsy starting at 4 years
have worked together of age until she died from cancer five years later.
since 1997 to support gery. “I thought I had brought her magnetic resonance imaging and/
home too soon after the surgery,” or cerebrospinal analysis may be
canine health research she says. used to rule out a brain tumor or
Heavily medicated on phenobarbital, other structural abnormalities.
to benefit all dogs. Pagan could hardly function and Idiopathic epileptic dogs may
Wingerter had no choice than to likely have a genetic predisposition,
stop taking her to obedience shows. and environmental factors may play a
“Adding potassium bromide and role in their disease. Seizures occur
reducing phenobarbital made all when abnormal brain functioning
the difference,” she says. “After a causes excessive or synchronous
couple of years working with my neuronal activity that goes beyond
veterinarian, the seizures stopped a normal threshold. Affected dogs
almost completely and Pagan started require lifelong antiseizure drug
traveling with me again. The experi- therapy, though the drugs don’t
ence is vivid even today though it’s generally eliminate all seizures. There
been 30 years. Pagan died at age 9 is no “one size fits all” protocol, thus
not from epilepsy but from cancer.” it takes time and experimentation
to find the right combination and
EPILEPSY INITIATIVE dosage for individual dogs.
PRIORITIZES RESEARCH Epilepsy is the most common
Idiopathic epilepsy affects about canine neurologic disorder and is
three-fourths of epileptic dogs, of ranked as one of the top health
which 20 to 30 percent are refractory, concerns of dog breeders and owners.
or resistant, to antiseizure drugs. A They worry about the impact of
veterinarian diagnoses idiopathic seizure frequency and severity on a
epilepsy after ruling out other brain dog’s quality of life, the side effects
diseases that can cause seizures. of antiseizure drugs and a potentially
Bloodwork is typically performed shortened life span.
first to evaluate a dog’s complete In 2017, the AKC Canine Health
blood count, chemistry profile and Foundation began its Epilepsy
bile acid levels for signs of organ Research Initiative to focus on better
dysfunction. If these are normal, understanding epilepsy and support-
4
ROTTWEILER Update
ing investigations of more effective Types of seizures seen in dogs are says. “Currently, it is unknown which
treatments. Altogether since its generalized tonic-clonic seizures (GTCS), antiseizure drug is more appropriate
beginning in 1995, the Foundation and non-generalized tonic-clonic for which type of seizure in dogs.”
has invested more than $2.8 million seizures (non-GTCS). A GTCS seizure
in support of 42 grants. In 2021, affects the whole brain and causes FUNCTIONAL MRI MAY
more than $375,000 was invested stiffening of the body (the tonic part), EXPLAIN PHYSIOLOGY
in epilepsy studies. making a dog fall to the ground, and OF EPILEPSY
Darin Collins, DVM, CEO of the convulsing, or rhythmic jerking of A new three-year study at North
Foundation, says, “Epilepsy is a the face and limbs (the clonic part). Carolina State University aims to
complex disease that affects pure- A non-GTCS seizure may be focal in better understand what causes
bred dogs and mixed breeds. It is nature affecting one-half or a small idiopathic epileptic seizures in dogs
frustrating that many dogs’ seizures part of the brain and causing altered using functional magnetic resonance
remain uncontrolled using the ther- awareness, such as a glassy or frozen imaging (fMRI) to evaluate brain
apies available today. We believe look, and/or affect the whole brain activity and measure small changes
that the research the Foundation is causing the tonic-clonic aspects of in blood flow associated with increased
funding with support from donors a GTCS seizure. energy demand. The study will include
and parent clubs will lead to inno- Dr. James explains that in veterinary 10 epileptic dogs not receiving anti-
vative approaches to deal with this medicine dogs are largely diagnosed seizure drugs and 10 neurologically
common disorder.” with epilepsy based on their owners’ normal dogs.
Here are highlights of three studies report of seizures and then prescribed Lead investigator Karen Muñana,
that are part of the 2021 portfolio and antiseizure drugs in a standard of care DVM, MS, DACVIM (Neurology),
an ongoing study. order. This is unlike human epilepsy professor of neurology, says, “We
standard of care where antiseizure hypothesize that these dogs with
A ‘REAL-TIME’ TEST TO drugs are prescribed based on the idiopathic epilepsy have alterations
UNDERSTAND SEIZURES seizure type. in the functional connectivity of the
The oftentimes mismatch between Inconsistencies between owners’ brain. Our goal is to better understand
the type of seizure a dog with epilepsy subjective descriptions of their dogs’ idiopathic epilepsy and potentially
has and the antiseizure drug used seizure episodes and results from develop more effective treatment
to treat the disease has prompted objective EEG testing create an strategies.”
a study just begun at the University underreporting phenomenon, partic- Whereas conventional MRI produces
of Guelph in Ontario, Canada. Lead ularly related to non-GTCS episodes, imagery of the anatomy of the brain
investigator Fiona James, DVM, DVSc, says Dr. James, citing a study she led revealing structural abnormalities,
DACVIM (Neurology), associate that was published in July 2021 in the fMRI captures information about the
professor, is using electroencepha- Journal of Veterinary Internal Medicine. brain’s activity. “Task-based fMRI is
lography (EEG), a technology that “We want to confirm the under- used widely in human medicine,”
evaluates brain function, to record reporting phenomenon and learn Dr. Muñana explains. “While an indi-
the electrical activity of the brain of how this impacts antiseizure drug vidual performs a task, he is being
affected dogs and aid in determin- therapy,” she says. “Our previous data scanned to identify the correspond-
ing the frequency of seizures and suggests that if antiseizure drugs ing regions of the brain that are
effectiveness of antiseizure drugs. make GTCS seizures more mild, they involved. Although task-based fMRI
The four-year study will evaluate could become non-GTCS seizures. has been used in dogs, it is challeng-
EEG recordings along with synchro- Owners may then undercount seizures, ing because awake dogs must lie still
nized video of about 160 dogs. “EEG which could mean we are overestimat- while unrestrained in the scanner as
is the only real-time test that can confirm ing the efficacy of antiseizure drugs images are acquired.
and classify different types of seizures when we evaluate them without EEG.” “An alternative known as resting
because it picks up the pattern of The ultimate goal of the study is to state fMRI can help identify structur-
electrical charge in a large population move the standard of care for vet- ally distinct but functionally related
of neurons,” Dr. James says. “Using erinary epilepsy patients closer to brain regions that are captured with
the EEG with synchronized video we human epilepsy standard of care. dogs in the resting state while under
can compare the patterns and frequen- “Identifying the best antiseizure drugs anesthesia,” she continues. “Resting
cy of seizures with the dog’s physical to use with particular seizure types state fMRI allows us to study the
manifestation and then evaluate the in dogs potentially will lead to more functional architecture of the brain
antiseizure drug therapy.” accurate seizure control,” Dr. James by detecting spontaneous fluctuations
5
SPRING 2022
in the brain’s blood flow. These become a powerful tool for investigating
fluctuations can be analyzed for the underlying cause of epilepsy in
synchrony to identify anatomically humans.
distinct but functionally connected “It holds similar promise in studying
regions of the brain known as rest- the disease in dogs,” says Dr. Muñana.
ing state networks (RSNs).”
In humans with epilepsy, alterations CBD AS AN ADJUNCT
in RSNs are associated with disease DRUG THERAPY FOR
progression, severity and treatment EPILEPTIC DOGS
response. Thus, resting state fMRI has A study showing the effectiveness
of cannabidiol (CBD) to significantly
reduce seizures in idiopathic epileptic
OWNERS OF ROTTWEILERS CAN HELP ADVANCE dogs that were also being treated
EPILEPSY RESEARCH with antiseizure drugs led to a new
Rottweiler owners are encouraged to participate in research that is part of study underway at Colorado State
the AKC Canine Health Foundation’s Epilepsy Research Initiative. Here University. The latest study focuses
is information about how to participate in the studies featured in this article. on learning the amount of an effective
• EEG & Video Study at the University of Guelph in Ontario, Canada: dose of oral CBD that will reduce
Recordings of 160 dogs will help to advance the accuracy of epilepsy monthly seizure activity by 50 percent
diagnosis and best therapies for seizure control. Contact Dr. Fiona or more when added to standard
James at epilepsy@uoguelph.ca or by calling 519-823-8830. antiseizure drug therapy.
• fMRI study at North Carolina State University: Evaluations of 10 epileptic “Epilepsy is a violent, emotional and
dogs not receiving antiseizure drugs and 10 neurologically normal devastating disease,” says Stephanie
dogs. Contact Julie Nettifee at janettif@ncsu.edu or by calling 919- McGrath, DVM, MS, associate pro-
513-6812. fessor, who leads the study. “The
• CBD study at Colorado State University: Assessing dose protocol and worst part is that in many dogs we
efficacy in idiopathic epileptic dogs. Contact Dr. Stephanie McGrath are not successful in treating this
at stephanie.mcgrath@colostate.edu or by calling 970-297-5000. disease or their quality of life is not
• Gut dysbiosis study at North Carolina State University: Evaluations of good. Sometimes we are successful
fecal samples of 100 pairs of housemate controlling seizures, but dogs must
dogs in which one is epileptic and the be euthanized due to the medication
other is unaffected: Contact Julie Nettifee at side effects. Alternative therapies are
janettif@ncsu.edu or by calling 919-513-6812. desperately needed.”
The potential benefits of oral CBD,
a cannabis-derived product made from
hemp that does not contain THC, the
psychoactive compound in cannabis
producing a high sensation, validates
its use in clinical trials to assess its
safety and efficacy and learn about
safe dosages. Although not yet approved
by the Food and Drug Administration
for use in veterinary medicine, CBD
is prescribed for humans as an adjunct
therapy for many diseases and for
pain management.
Enrolled dogs in this study will
participate for three months during
which three doses of CBD will be
evaluated to learn which is most
effective. Dogs will first receive milli-
grams of oral CBD per kilogram of
body weight every 12 hours, then
6
ROTTWEILER Update
5 milligrams per kilogram of body The four-year study aims to better cally found in the GI tract of humans,
weight and finally 10 milligrams per understand refractory epilepsy in are believed to have a beneficial
kilogram of body weight. Participants which 20 to 30 percent of dogs are effect. Although not yet linked to
will be rechecked at four-week intervals. resistant to antiseizure medications. epilepsy, a decrease in Lactobacillus
“We need to home in on the appro- Molecular genetic analysis, a method populations is believed to contribute
priate dose for individual dogs, as it called 16S gene amplicon sequencing, to the development of human
likely varies by age, seizure frequency is being performed on fecal samples neurologic diseases such as anxiety
and breed,” Dr. McGrath says. “Candi- from the pairs of housemate dogs to and depression, autism spectrum
dates for this study are dogs having learn about differences in specific disorders, multiple sclerosis, and
two or more idiopathic epileptic bacterial populations of epileptic Alzheimer’s disease.”
seizures a month for a minimum of dogs and the control dogs. The study will aid understanding
12 weeks after being treated with a Participating dogs not only must of the complex signaling between
least one antiseizure drug. Participants live in the same household, they also the GI tract and the nervous system
will undergo a complete seizure must be fed the same diet. “By com- — the microbiota-gut-brain axis. “Our
workup that includes a neurological paring results from pairs of dogs hope is that this study will advance
examination, bloodwork, brain MRI, within the same household that are understanding of epilepsy and drug
and cerebrospinal fluid analysis.” fed the same diet, we aim to minimize resistance and guide the development
Besides determining CBD dosage the effects of diet and environment, of improved seizure control for dogs
protocol, Dr. McGrath says this study which have been shown to have an with epilepsy,” she says.
will continue evaluating the safety effect on the composition of the gut Collectively, these investigations that
and tolerability of CBD in dogs with microbiome,” Dr. Muñana says. “This are part of the Epilepsy Research
idiopathic epilepsy. “CBD has the will provide a more accurate analysis Initiative offer promise of better un-
potential to improve the quality and of differences in the gut microbiome derstanding this frustrating disease.
length of life for dogs with uncon- that may be due to epilepsy itself.” Dice, the Rottweiler male who first
trolled epilepsy while adding a The hypothesis is that dogs with experienced idiopathic epileptic
much-needed tool for veterinarians idiopathic epilepsy have alterations seizures last May, may one day ben-
treating canine epilepsy,” she says. in intestinal bacteria. “We want to efit from new treatments that come
determine if dogs with idiopathic from these studies.
STUDYING GUT DYSBIOSIS epilepsy have shifts in their gut Meanwhile, his owner, Raquel Burke,
IN EPILEPSY microbial populations such as the says, “We’ve been diligent about the
A disruption of the delicate balance presence of Helicobacter and a timing of Dice’s medications and
of the gut microbiota, known as gut decrease in Lactobacillus that result monitoring his seizures. We have a
dysbiosis, could play a role in canine in inflammation associated with camera that captures his movements
idiopathic epilepsy. A study of 100 epilepsy,” says Dr. Muñana. so we can show video recordings of
pairs of dogs living in the same A common organism in the human his seizures to our veterinarians.
household — an epileptic dog that is gastrointestinal tract, Helicobacter “Dice is a lover boy who has never
untreated or treated with the antiseizure in most cases does not cause clinical met a stranger. He loves to sit and be
drug phenobarbital and an unaffected disease. When clinical signs are petted. I do barn hunt and trick dog
dog — aims to learn if there are differ- present with H. pylori, they most with him. Most importantly, I’ve
ences in the gut microbiome linked often cause stomach disease. In learned to let him enjoy life and
to idiopathic epilepsy. addition, in some people infection take it a day at a time as is best
Dr. Muñana of North Carolina State with H. pylori has been linked to the with canine idiopathic epilepsy.” n
University, the lead investigator, says, development of neurologic disorders,
“We believe there is an important including Alzheimer’s disease, multiple
Purina thanks the Rottweiler Health
interaction between the GI tract and sclerosis, Parkinson’s disease, and
Foundation, particularly president
the brain that is vital for maintaining ischemic stroke. It is also believed that
Roberta Kelley-Martin, for helping
normal homeostasis of the nervous H. pylori may play a role in epilepsy.
us to identify this topic for the
system and that can influence a dog’s Meanwhile, Dr. Muñana says, “Lacto-
Rottweiler Update.
susceptibility to epilepsy.” bacillus organisms, which also are typi-
LOOKING TO REPRINT? Rottweiler Update articles may be reprinted provided the article is used in its entirety and in a positive
manner. To request permission to reprint this article, please contact the editor at: Barbara.Fawver@purina.nestle.com. Reprints
should include the following attribution: Used with permission from the Rottweiler Update, Nestlé Purina PetCare.
7
ON LY ON E
BRAND FUELS
OF TH E TOP
SHOW D OGS
SEE WHY CHAMPIONS
CHOOSE PURINA® PRO PLAN®.
SUPPORTS HELPS KEEP HELPS OPTIMIZE
IMMUNE SYSTEM SKIN & COAT OXYGEN METABOLISM
DURING TRAVEL IN EXCELLENT FOR INCREASED
& COMPETITION CONDITION STAMINA
proplansport.com
EXCLUSIVELY AT P ET SP ECIA LT Y A N D ON L IN E R ETA I L E R S
*Dog News Magazine Top 100 Dogs based on AKC All-Breed Competition and RBIS through 12/31/20.
The handlers or owners of these champions may have received Pro Plan dog food as Purina ambassadors. Purina trademarks are owned by Société des Produits Nestlé S.A.You can also read
