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Category: NERVOUS SYSTEM (epilepsy, auditory, nerves, spinal cord, brain, etc.)
Author: Sharon M. Albright, DVM, CCRT Source: AKC Canine Health Foundation
Despite appropriate treatment with anti-seizure medications, one-third of epileptic dogs continue to have seizures. The side effects of anti-seizure medications and the behavioral changes that often accompany canine epilepsy (anxiety and cognitive decline) lead to a decreased quality of life for affected dogs and their owners. For these reasons and more, the AKC Canine Health Foundation (CHF) and its donors are investing in research to explore new treatment options for canine epilepsy. Read more…
Understanding Canine Epilepsy
Canine Health Foundation, June 2014 Introduction
Epilepsy is the most common neurological disease seen in dogs, affecting up to five percent of the canine population (3,4). However, this statistic is somewhat misleading as epilepsy is not a single disease. Instead, the diagnosis of epilepsy potentially refers to any one of a number of conditions that are characterized by the presence of chronic, recurring seizures. These conditions may be inherited (genetic, primary or idiopathic epilepsy), caused by structural problems in the brain (structural or secondary epilepsy), result from metabolic problems or a toxic exposure (reactive epilepsy), or stem from an unknown cause (4). Determination of an appropriate treatment regimen for canine epilepsy depends on an accurate diagnosis of the type and cause of seizures, only after which appropriate therapeutic options can be identified. Read full article…
Beagles Are Among Breeds Prone To Steroid-Responsive Meningitis-Arteritis
Fall 2019 (Used with permission from the Beagle Update, Nestle Purina PetCare.)
Given his handsome looks and outgoing charm, “JR” (GCH Pun Kotzky Jolly Roger Of Sunbriar CD BN RA CA TKI), a 15-inch tricolor male Beagle, easily finished his show championship title. When he was 2 1/2 years old, JR earned an invitation to the Top 20 competition at the 2015 National Beagle Club (NBC) National Specialty.
Months before the National, JR started to limp in his right rear leg and seemed “out of sorts,” recalls owner Brett Sprout of Alliance, Ohio. Soon he recovered and resumed his winning ways only to become suddenly lame again, this time favoring his right front leg.
“The veterinarian thought that JR had an orthopedic problem affecting his legs,” Sprout says. “He took X-rays of JR’s legs and had a specialist examine him. They posted JR’s radiographs on VetRad, a teleradiology internet site for veterinarians, hoping someone would offer clinical suggestions. No one provided feedback.”
Meanwhile, JR’s limping continued to come and go. “One day he would seem all right, and then the lameness would return,” says Sprout.
Sadly, JR missed the 2015 National Specialty because he was too lame to compete and seemed to be in pain. “We were beginning to think JR was on a path leading to a bad end,” Sprout says. “It appeared that he was not enjoying life.”
Sprout and his wife, Susan, attended the National Specialty that year at Purina Farms in Gray Summit, Missouri, without JR. Querying fellow Beagle owners about JR’s mysterious condition, Sprout wasn’t getting anywhere — until he talked to Darlene Stewart, chair of the NBC Health and Genetics Committee. That conversation may have saved JR’s life.
“Darlene homed in on a likely cause of the problem, and the more we talked, it seemed more and more plausible,” Sprout says. “As she described ‘Beagle pain syndrome,’ an inflammatory neurological disorder in dogs now known as steroid-responsive meningitis-arteritis (SRMA), it seemed that this could be the diagnosis. As it turns out, Beagles are among the breeds predisposed to developing this condition.”
When the Sprouts returned home, they shared the information with JR’s veterinarian. After confirming that SRMA was a likely cause of JR’s pain, the veterinarian began treatment with a corticosteroid, prednisone. Within a day, JR was better.
“We were concerned that JR’s pain was becoming unbearable and we might have to euthanize him, but after treatment he became a new dog,” Sprout says.
Stewart (AlaDars) of Theodore, Alabama, was no stranger to SRMA. Nearly two decades earlier, her 14-month-old 15-inch tan-and-white female Beagle, “Sandi” (CH AlaDars Sandwitch), started moving hesitantly as if in pain in her shoulders or neck. The veterinarian began treating her with steroids for a perceived disc disorder. Sandi responded well, so the cycle of treating her with steroids for intermittent pain continued for many years.
At age 8, Sandi suffered a severe bout of pain and was so unresponsive to treatment that euthanasia seemed the only choice. Desperate for answers, Stewart scoured the veterinary literature and found an obscure article describing signs that fit Sandi perfectly. Her veterinarian followed the suggested treatment, and Sandi improved within a day.
“She never had another severe episode, but at the first sign of her ‘headache look’ I would start her on prednisone for about a week,” Stewart says. “Sandi lived to be 16 and ultimately died of cancer.”
Through the years, Stewart has heard many stories of Beagles experiencing clinical signs and pain similar to Sandi. The typical scenario is a young hound that suddenly develops acute neck pain and lethargy that may progress to whole body pain and often includes lameness and fever. Veterinarians initially presume a dog has suffered an injury or may diagnose disc disease or bacterial infection. Chronic cases may develop other neurological deficits, such as incoordination or weakness of the limbs.
The disorder originally was known as Beagle pain syndrome because it was first recognized in Beagles exhibiting signs of pain, lameness and fever. An article published in 1989 in Toxicological Pathology on these dogs reported that veterinarians at Cornell University suspected this was an unusual syndrome in Beagles and that cases as far back as 1973 seemed to match Beagle pain syndrome. In the 1990s, several large-scale studies reported on the syndrome occurring in various breeds. Once such study was published in 1994 in the Journal of Small Animal Practice.
The good news is that the pain and other clinical signs of the disease resolve with treatment. Antibiotics and rest are not effective in treating dogs with SRMA. Rather, it is the anti-inflammatory benefits of corticosteroids that help to resolve the clinical signs of SRMA. Not a lot is understood about the cause of SRMA, but it is believed to be an immune-mediated condition.
A NEUROLOGICAL DISEASE
“Steroid-responsive meningitis-arteritis is a common inflammatory disease of the nervous system of dogs involving the meninges, or membranes that cover the brain and spinal cord, and associated arteries,” says Karen Muñana, DVM, MS, DACVIM (Neurology), professor of neurology at North Carolina State University. “Clinical signs are resolved in most dogs with treatment, but relapses may occur as treatment is tapered or discontinued. Little is known about what triggers SRMA.”
A recently completed study at North Carolina State University evaluated clinical and treatment differences among breeds of dog with acute SRMA and surveyed owners to learn about the quality of life of affected dogs. The research, led by neurology resident Jeanie Lau, BVSc, working with mentor Dr. Muñana, was funded through the AKC (American Kennel Club) Canine Health Foundation Clinician-Scientist Fellowship program.
“The AKC Canine Health Foundation was excited to support this important research, and we are thankful to the breeders who participated in the study,” says Dr. Diane Brown, CEO of the AKC Canine Health Foundation. “We are interested in further supporting investigations into this disorder of young dogs and raising awareness among breeders and the veterinary community.”
“Our retrospective study included 61 dogs,” Dr. Lau says. “We sent an online survey to the owners of 29 dogs identified through an AKC Canine Health Foundation survey and 32 dogs treated at the North Carolina State Veterinary Hospital. Among the questions, we asked owners to rate their dog’s quality of life during treatment, during clinical resolution and since being diagnosed with SRMA.”
The first study of SRMA in dogs in the U.S., the research was published online in the June 7, 2019, issue of the Journal of Veterinary Internal Medicine. The study provided insightful information that included identifying two breeds not previously recognized as being susceptible to SRMA — Golden Retrievers and Wirehaired Pointing Griffons. A review of the medical records of affected dogs looked at their age, breed, sex, neuter status, body weight, length of time between clinical signs and treatment, duration of treatment with corticosteroids, and results of additional diagnostic tests.
All dogs in the study experienced lethargy and neck pain. Many also had decreased appetite and were reluctant to rise or walk and had a stiff gait. Some dogs had a crouched posture or tremors. About three-quarters of the dogs had fever, and 38 percent of dogs had a temperature greater than 104 degrees Fahrenheit.
The study charted four outcomes: 1) clinical resolution, 2) relapse, 3) clinical remission, or 4) death for reasons unrelated to SRMA. A relapse was defined as recurrent clinical signs that resolve completely after treatment with an increased dosage of corticosteroids and the addition of a second immunomodulatory drug or both. Clinical remission was the absence of clinical signs after beginning corticosteroid treatment, and clinical resolution was the absence of clinical signs after completing corticosteroid treatment.
“We asked owners to rate their dogs’ quality of life on a scale of one to 10, with one being poor and 10 being excellent,” Dr. Lau says. “The mean quality of life for dogs during treatment was significantly worse than during clinical resolution and since being diagnosed with SRMA. This was associated with the severity of prednisone’s adverse effects. When we asked owners to assess the severity of their dogs’ neck pain at onset, around 77 percent noted improvement of clinical signs within one to two days of starting prednisone.”
Among the negative effects owners noted about continued use of prednisone were: polydipsia (excessive thirst), polyuria (excessive urination), polyphagia (excessive hunger), panting, weight gain, thinning of hair coat, restlessness, sleeping more than usual, inappropriate urination, “pot belly” appearance, development of non-dermatological infections, diarrhea, dermatitis, and vomiting.
“Any breed can develop SRMA, though a predisposition was previously recognized in several breeds,” Dr. Muñana says.
Breeds previously considered predisposed include: Beagle, Bernese Mountain Dog, Border Collie, Boxer, English Springer Spaniel, Jack Russell Terrier, Nova Scotia Duck Tolling Retriever, Weimaraner, and Whippet. The two newly recognized breeds prone to SRMA were highly represented in the study. Golden Retrievers had the highest incidence with 12 dogs affected, and Wirehaired Pointing Griffons had the third-highest incidence with nine dogs affected. Other breeds with a high prevalence were: Bernese Mountain Dogs with 10 dogs affected, Boxers with nine dogs affected, and Beagles with six dogs affected.
“Our findings suggest that Golden Retrievers and Wirehaired Pointing Griffons should be included among breeds recognized to develop SRMA,” says Dr. Muñana. “Golden Retrievers were included in a previous study of SRMA, but Wirehaired Pointing Griffons had not been previously described with SRMA.
“Further, we saw that the Wirehaired Pointing Griffon had a significantly higher number of prednisone-related adverse effects compared to other breeds. This is likely because they were treated with substantially higher prednisone dosages when compared to Beagles, Bernese Mountain Dogs and Golden Retrievers. It also could be due to the difference in their lifestyle as a hunting breed or could reflect an increased genetic susceptibility to corticosteroid-related adverse effects.”
SRMA typically affects dogs from 6 to 18 months of age. The median age at which dogs in the North Carolina State study were diagnosed was 8.5 months, with 95 percent of dogs being under 2 years of age. The study comprised 34 males, 18 intact and 16 neutered, and 27 females, six intact and 21 spayed.
“Diagnosis is based on increased numbers of neutrophils, a type of white blood cell, in the cerebrospinal fluid (CSF) of affected dogs and exclusion of other infectious diseases combined with a positive response to corticosteroids,” Dr. Muñana says. “Some neurologists use magnetic resonance imaging (MRI) to rule out clinically similar conditions, such as intervertebral disc disease, though an MRI is a costly procedure and is not required to diagnose SRMA, particularly in a young dog with signs typical of SRMA.”
A newer noninvasive, more affordable test involves measuring the level of C-reactive protein (CRP), a substance produced by the liver in response to inflammation in the blood serum indicating systemic infection. In affected dogs, the CRP level is elevated parallel to that of neutrophils in CSF.
“CSF analysis is useful for an initial diagnosis followed by CRP analysis to monitor a dog’s response to therapy,” Dr. Muñana says. “Since therapy is associated with side effects, some of which can be quite serious, I do not recommend treatment unless it is supported by a diagnosis.”
The most effective treatment for dogs with SRMA is immunosuppressive dosages of corticosteroids given over several months. “Most dogs improve dramatically within one to three days, then continue on daily high doses of prednisolone or prednisone for four to eight weeks, though some dogs may continue treatment for six months to a year,” says Dr. Muñana. “During this time, dogs should have regular blood work to ensure they are tolerating the steroid therapy and to monitor CRP levels.”
The long-term prognosis for young dogs with acute SRMA is fair to good. Most dogs — at least 80 percent — respond well to the initial course of steroids. About 10 to 15 percent relapse during treatment, and about 20 to 30 percent relapse in the month following discontinuation of treatment. A few dogs will relapse over a year after treatment ends. Some dogs require lifelong therapy.
Whereas acute cases respond well, chronic SRMA is more challenging to treat, says Dr.Muñana. “Chronic SRMA develops in dogs that are not diagnosed and treated in a timely manner or that have recurring relapses. Chronic cases have fewer CSF abnormalities than dogs with acute SRMA, but the abnormalities are consistent with chronic infection. Their treatment is the same — high-dose immunosuppressive corticosteroids, and a second immunosuppressive drug is usually needed.”
“Our research included identifying factors associated with the frequency of relapses and owners’ assessments of the severity of relapses in the 29 dogs that relapsed,” Dr. Lau says. “Among the variables we studied were the age at onset of clinical signs, prednisone dosage and treatment duration, treatment with a second immunomodulatory drug at initial diagnosis, and duration between onset of clinical signs and initiation of treatment.”
Treatment results on prednisone were excellent, with 29 dogs having complete resolution of clinical signs for a median of 37 months. In 25 dogs, remission was achieved, thus they began a tapering schedule to reduce prednisone at follow-up. One dog was euthanized due to developing neurological problems during relapse.
As with the success JR and Sandi experienced, treatment results show that dogs with SRMA have an excellent prognosis for remission and a fair to good prognosis for resolution, with remission and resolution rates of 98.4 percent and 54 percent, respectively. “Most dogs experience improvement within 48 hours of beginning treatment,” says Dr. Muñana.
Reflecting, Dr. Lau says, “As a retrospective study, this had several limitations including that the accuracy of the completeness of the data collected was dependent on the information available in the dogs’ medical records. We also were limited in the numbers of particular breed cases, and this restricted the power of the study.”
Many questions remain. “I think the most pressing questions involve determining optimum treatment and the cause of SRMA, including whether there is a genetic basis,” Dr. Muñana says. “Our team feels further investigation is warranted to learn the influence of individual breeds on disease severity and its clinical course and how it impacts a dog’s quality of life.”
Meanwhile, Sprout’s hound JR has rebounded and resumed a busy performance career. At the 2017 NBC National Specialty, JR earned High in Trial in obedience with a score of 194, and he made the final cut for Best of Breed. At the 2018 and 2019 Rally National Championships, JR was the highest-scoring Beagle.
“We recently started JR in agility, and he has already earned two Q’s out of two attempts,” Sprout says proudly. “Plus, he is a bronze Grand Champion. Everything he has achieved has been possible thanks to a conversation with Darlene Stewart at the 2015 National.”
Purina appreciates the support of the National Beagle Club, particularly Darlene Stewart, chair of the Health and Genetics Committee, for helping us to identify topics for the Beagle Update.
CLINICAL SIGNS OF STEROID-RESPONSIVE MENINGITIS-ARTERITIS IN DOGS*
Reluctance to rise or walk
*Source: Lau J, Nettifee JA, Early PJ, et al. Clinical Characteristics, Breed Differences, and Quality of Life in North American Dogs with Acute Steroid-Responsive Meningitis-Arteritis. Journal of Veterinary Internal Medicine. 2019;33(4):1719-1727.
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Beagle 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 Beagle Update, Nestlé Purina PetCare.
Steriod Responsive Meningitis (SRMA OR SRM)
Animal Health Trust (Added 9/2017)
Steroid responsive meningitis arteritis (SRM or SRM) is a systemic immune disorder characterised by inflammation of the meninges and the associated arteries that typically responds to corticosteroids. SRM is also known by other names such Beagle pain syndrome, necrotizing vasculitis, juvenile polyarteritis syndrome, cortico-responsive meningitis, aseptic suppurative meningitis and sterile purulent meningitis, which sometimes generates confusion among owners and veterinary surgeons alike. The name steroid responsive meningitis arteritis is well established in the veterinary literature and best describes the clinical and pathological features of the disease.
SRM is over represented in Beagles, Boxers, Bernese Mountain dogs, Weimaraner, and Nova Scotia duck tolling retriever, which suggests the possibility of a genetic predisposition. Other young medium to large breed dogs may also be affected.
Age of onset typically is between six and 18 months with a range from four months to seven years old. The condition can either be acute or chronic and the clinical signs are characterised by episodes of profound spinal pain, depression, stiff gait and fever. These episodes result from a combined inflammation of the meninges and the meningeal arteries. Occasionally SRM occurs with immune-mediated polyarthritis, especially in Bernese Mountain dogs, Boxers and Akitas which causes pain and swelling of the joints.
There is not a definitive test for identification of SRM. Clinical diagnosis is based on the clinical presentation, history, and physical and neurological examination, in conjunction with specific blood tests, cerebrospinal fluid analysis and advanced imaging. These tests are required to rule out other diseases that may present with similar clinical signs especially as in some of the diseases corticosteroids may be contraindicated and detrimental to the patient.
Treatment with immunosuppressive dose of corticosteroids in cases of SRM usually results in rapid improvement, although there are refractory or chronic cases that require a second immunosuppressive drug. The treatment is long term and once the clinical signs are controlled, the dose of medication is decreased over months (usually a minimum of four months). The immunosuppressive treatment requires close monitoring by a veterinary surgeon, who decides, based on different examinations and diagnostic tests, when the medication can be decreased and finally discontinued. The prognosis for recovery is good but the potential for relapse exists.
In 2010 the Canine Genetics team at the AHT, funded by generous donations from several Beagle Clubs from around the country and from many individuals, conducted a study into SRM in Beagles. A whole genome association scan was carried out on DNA samples from 47 Beagles (26 affected cases and 21 control cases). This type of scan allows us to compare the genomes of dogs affected with SRM to the genomes of healthy dogs (control cases) and to pinpoint any regions where a clear difference can be seen. Such regions are likely to be associated with the disease and may contain mutations in genes that are involved with SRM.
Although the genotyping was carried out successfully, the study failed to identify any regions of the genome which were clearly and significantly associated with the disease. The genotyping data we generated was of high quality, so the likely explanation of our failure to identify a region of the genome associated with SRM is because the disease is more complex than was originally thought. This is either because SRM is caused by more than one gene, or the interaction between genes and the environment. In either of these cases the solution is to collect and genotype more samples, and any new data can be added to what we already have, thus increasing the chances of success.
This is a disappointing result in some ways, but as a result of this investigation we now can say fairly confidently that SRM in the Beagle is not inherited as a simple autosomal recessive disease with a high degree of penetrance, and that more samples need to be analysed to identify a genomic region associated with the disease.
Since then we have been collecting additional samples for a larger study, and in 2013 we achieved our target of collecting enough samples for a study with 48 cases and 48 controls. We also successfully applied for a grant from the Petplan Charitable Trust to carry out some of this work, and during 2014 we will be undertaking this new study.
Definition of cases and controls
To study any disease we require DNA samples from dogs that are affected with the disease (‘cases’) and also dogs of the same breed that are unaffected (‘controls’).
An affected case of SRM is defined as a dog that has been examined by a veterinary surgeon and based on clinical examination and diagnostic tests is suspected to have the disease.
A control case of SRM is defined as a dog over five years of age that has never had any of the clinical signs compatible with SRM.
Preferably, we would also require copies of examinations and diagnostic tests done by the veterinary surgeon in charge of the case.
These posts offers useful links to website covering the NERVOUS SYSTEM that include auditory, nerves, spinal cord, brain, Epilepsy, etc.
RVC research finds potential in ground-breaking new dietary treatment for canine epilepsy, Royal Veterinary College University of London, May 14, 2020. Funded by the American Kennel Club Canine Health Foundation. Learn more…
Ketogenic Diet Linked to Seizure Reduction in Dogs with Epilepsy
By Amy Karon, DVM, MPH; July 15, 2016 Learn more…
VEDA: Vestibular Disorder.
ABOUT: We Help People Find Balance. Balance is easily taken for granted. However, when the fragile vestibular organs of the inner ear are damaged by illness or injury, anyone can lose the ability to balance—not just physically, but the demands of school, work, family, and independent living. These profound impacts are often made worse by the disorder’s invisibility to others and the extended amount of time it takes to get an accurate diagnosis. Learn more…
VCA: Vestibular Disease in Dogs
By Ernest Ward, DVM December 11, 2008 Click Here
Vestibular Disease in Dogs & Cats
By Vestibular Disorders Association Click Here
Investigating Dietary Supplements for the Treatment of Canine Idiopathic Epilepsy (03/15/2019)
Author: Sharon M. Albright, DVM, CCRT Learn more….
Slipped Disc, Bad Back, and Muscle Spasms in Dogs: Source: petMD Learn more…
Epilepsy in the Petit Basset Griffon Vendeen: Prevalence, Semiology, and Clinical Phenotype
J Vet Intern Med 2011
By C.H. Gulløv, N. Toft, M.M.N. Baadsager, and M. Berendt Learn more…
By Edward (Ned) E. Patterson, DVM, PhD
Vet Clin Small Anim 44(2014) 1103-1112.
Epilepsy is a disorder of the brain that is characterized by recurring, unpredictable seizures. The seizures are likely due to uncontrolled electrical activity in regions of the brain, which can produce behavioral changes. When no specific cause for the seizures can be found, the disease is known as idiopathic epilepsy (IE). Young dogs (less than 1 year of age) that experience seizures often do so because of exposure to an infectious agent or to a developmental anomaly. However, the seizures could also be due to an inherited degenerative disease or metabolic disorder. Most dogs that experience their first seizure when they are much older than 5 years of age most commonly do so because of a tumor, or a late-onset degenerative or metabolic disorder. IE is the diagnosis when a specific cause for the seizures cannot be found. It typically occurs in between these very early and late cases, with an age of onset between 1 and 5 years. IE is only diagnosed after all other causes of the seizure activity have been ruled out. Most dogs with IE have a normal lifespan. However, dogs that experience seizures lasting at least five minutes or who have multiple seizures without recovery in between (known as status epilepticus) typically have a reduced survival time.
Dr. Ned Patterson is an epilepsy clinician and researcher at the University of Minnesota Clinical Investigation Center. His Canine Epilepsy Network (www.canine-epilepsy.net) is a wonderful online resource for owners and breeders of affected dogs, as well as clinicians and researchers. He gave an excellent health seminar on epilepsy at the 2009 PBGVCA National in Tucson.
In this recent article, Dr. Patterson focuses on the need for urgent and aggressive treatment for seizures that last more than a few minutes or occur back-to-back without recovery. He cites the statistic that 40 to 60 percent of dogs with idiopathic epilepsy suffer cluster seizures or status epilepticus. These are emergencies that can lead to irreversible neuronal damage. Prolonged or frequent seizures can also lead to heart and kidney damage.
Dr. Patterson outlines the general standard of practice for canine status epilepticus. Unfortunately, there has not been an expert panel consensus statement for treatment of the canine disease, as there has been for human status epilepticus. Dr. Patterson states, “There does seem, however, to be fairly similar recommendations from a number of sources that can be generally summarized as:
“1. First-line therapy should be with a benzodiazepine, which most often is intravenous diazepam, but can be by other routes and/or with midazolam, or lorazepam. There have not been any published studies comparing benzodiazepines to each other in dogs or cats as there has been for people. Shortly after the benzodiazepine, there should be intravenous loading or mini loading doses of intravenous phenobarbital or intravenous [levetiracetam] to start chronic therapy, for when the short-acting benzodiazepines wear off.
“2. In second-line therapy for continuing seizure activity, intravenous phenobarbital or intravenous LEV or a [constant rate infusion] of diazepam or midazolam should be given. The author has found that two or more of these second-line therapies can potentially be given to the same patient.
“3. Third-line therapy of [refractory status epilepticus] to induce general anesthesia can be with intravenous propofol or pentobarbital. In some instances, IV ketamine or inhalant anesthesia has been administered.”
Research over the past decade has tested new approaches, which Dr. Patterson hopes will lead to paradigm shifts in treatment for seizures. These include neurosteroids, gene therapy, use of molecules that alter gene expression, and new biochemical targets. Dr. Patterson concludes, “Status epilepticus in companion animals is an emergency and should be quickly treated by recommended first-line (emergent) therapy with benzodiazepines followed by loading doses of chronic therapy drugs, and then secondline, and third-line (refractory) therapy when needed. Cluster seizures can evolve into status epilepticus, and therefore at-home treatment with per rectum or intranasal benzodiazepines and longer-acting oral antiepileptic drugs for dogs is often recommended, and if not effective, then hospitalization for observation and treatment as for status epilepticus are recommended.”