When is a canine seizure a brain tumor?

Boxers, along with other brachys, are among the most common breeds to develop gliomas, tumors of the supportive cells of the brain and represent a major category of primary brain tumors. It is a normal day in your general practice clinic. You’ve had a steady, booked schedule of mainly wellness exams with a smattering of dietary indiscretion and endocrinopathies. Your final appointment before your lunch break is for an eight-year-old neutered male boxer. You have seen this dog, Champ, for every annual exam and various mild maladies. Today’s presenting complaint: possible seizures. Your technician rooms Champ and his owner. She returns shortly after with a history and Champ’s vitals. The owner tells you Champ had an episode at home about one week ago. It came out of nowhere while he was sleeping. He became rigid and then started convulsing. He had a glazed look. He was drooling profusely. The episode lasted for about 90 seconds. Afterward, he seemed anxious for several hours. Champ had another such episode three days later. He has not had any since, and his owner was going to cancel today’s appointment, but she figured it was worth having him examined. You enter the exam room to find Champ sitting next to his owner, looking alert and overtly normal. On his general physical examination, all you find is that he is mildly over-conditioned. His owner asks you what could have caused the episodes. You pause. “What could have caused the seizures in Champ, and how can I figure it out?” You excuse yourself from the exam room in order to refresh your knowledge before answering her question. What causes seizures in dogs? Seizures always neurolocalize to the prosencephalon (the cerebrum and the thalamus). Broadly, seizure differentials are broken into extracranial and intracranial causes, along with idiopathic epilepsy. Idiopathic epilepsy is the most common cause of seizures in dogs. Generally, though, it leads to seizures starting between six months to six years of age. Dogs with epilepsy are completely normal in between their seizures. Extracranial causes of seizures include metabolic conditions and toxins. Intracranial causes of seizures include degenerative diseases, anomalous conditions, neoplasms, infectious diseases, non-infectious inflammatory diseases, and vascular conditions. A thorough list of extracranial and intracranial differentials by category is provided in Table 1. Table 1. Differentials for seizures in dogs. Idiopathic epilepsy is the most common cause of seizures in dogs but is a diagnosis of exclusion when extracranial and intracranial differentials have been either definitively or presumptively ruled out. How can I create a list of differentials for Champ? A critical first step is performing a complete neurological exam. A normal exam is less helpful in ranking differentials than an abnormal one. Following the examination, differentials should be ranked with consideration toward the patient’s signalment and history. For example, a portosystemic shunt is a much more likely cause of seizures for a four-month-old Yorkshire terrier than for a 10-year-old Labrador retriever. You realize you have yet to perform a full neurological exam on Champ, so you return to the room. You ask Champ’s owner if you can bring Champ to your treatment area and she obliges. Performing the neurological exam The neurological exam can be broken into hands-off and hands-on sections. In a patient with seizures, and, therefore by default, a neurolocalization of the prosencephalon, evaluating the patient’s mentation, how they navigate the room, postural reactions, and cranial nerve testing will be the most informative parts of the exam. On exam, Champ appears mentally normal. You let him have free range of the room. You notice that although he does not have any overt gait abnormalities, he is walking in circles to the right. You never observe him turn to the left. When you do his postural reactions, you observe he does well in his right limbs, but has severely delayed postural reactions in his left limbs. On his cranial nerve exam, you observe he lacks a menace response in the left eye and also does not react when you poke the left side of his nasal septum. The rest of his neurological exam is normal. Where does Champ’s neurological exam neurolocalize? You already know Champ’s seizures neurolocalize to the prosencephalon. Yet, which side has the problem? Champ’s propulsive circling to the right points to a lesion affecting his right prosencephalon. Unilateral lesions lead to circling toward the lesion due to a condition called “hemineglect.” His left-sided postural reaction deficits, menace deficit, and nasal hypalgesia also fit with a lesion in the right prosencephalon. This is because the right prosencephalon processes the kinesthetic information from the left limbs as well as the left visual field and left facial sensation. Armed with your complete exam, you can refine your list of differentials and provide Champ’s owner with an answer to her question. Lesions that “lateralize,” as in Champ’s case, point to a structural problem in the brain. This means idiopathic epilepsy is immediately struck off the list of differentials for Champ. Extracranial differentials are also struck off the list, as they do not exert their effects on only one side of the brain. The same applies to degenerative diseases within the intracranial category. This leaves conditions within the anomalous, neoplastic, infectious, non-infectious inflammatory, and vascular categories. Champ is too old for an anomalous condition, such as hydrocephalus, to be the cause of a new onset of seizures. Infectious diseases are very unlikely, especially in a fully vaccinated dog. Non-infectious inflammatory diseases, broadly referred to as meningoencephalitis of unknown etiology, can cause a lateralizing prosecephalic disease, but Champ is the wrong breed. A stroke is certainly a possibility as the cause of Champ’s signs, especially considering they do not seem to be getting worse. Unfortunately, a cancerous cause is the most likely reason for Champ’s seizures. What types of brain tumors do dogs get? Brain tumors are divided into primary brain tumors and secondary, or metastatic, brain tumors. Primary brain tumors consist of meningiomas, glial cell neoplasms, ventricular tumors, and pituitary neoplasms. Glial neoplasms are further divided into astrocytomas and oligodendrogliomas. Brachycephalic breeds are most likely to develop glial neoplasms. Various breed patterns are summarized in Table 2. Secondary brain tumors metastasize from elsewhere in the body. The most common metastasis to the canine brain is hemangiosarcoma (Mallol et al. 2021). Other metastases include histiocytic sarcoma, lymphoma, melanoma, and various carcinomas (Miller et al. 2019). In general, different tumor types do not lead to different presentations; if a tumor is affecting the prosencephalon, for example, it can cause seizures and neurological deficits referable to a lesion in the prosencephalon. Likewise, tumors in the brainstem lead to deficits referable to a lesion in the brainstem regardless of the tumor type. Different tumor types and tumor locations do have different treatment options as well as different outcomes, though. Why is a brain tumor the most likely cause of Champ’s right prosencephalic lesion? There are a couple of reasons why this is the most likely differential for Champ: 1) His age and breed align with brain tumor development. Any dog breed can develop a brain tumor, but dogs are usually at least six years old, and boxers are one of the most common breeds to develop gliomas. Gliomas are tumors of the supportive cells of the brain and represent a major category of primary brain tumors. A recent study showed in boxers specifically, a primary brain tumor was often the cause of seizures, even in dogs less than six years old (Loncarica et al. 2022). 2) He is having seizures. Seizures are the most common first sign of a brain tumor in dogs. Champ’s neurological examination was abnormal, which only heightens suspicion of a brain tumor. However, many brain tumor-bearing dogs have completely normal neurological exams with a new onset of seizures as their only clinical sign, until the tumor reaches a size large enough to cause observable abnormalities, as in Champ’s case. You let this likely differential sink in, and realize that Champ’s owner is immediately going to want to know how to confirm your suspicion, what treatment options are available, and how long Champ will survive with a good quality of life. So, you continue reading. How are primary brain tumors diagnosed in dogs? The best way to confirm a primary brain tumor in dogs is with magnetic resonance imaging (MRI) of the brain. Computed tomography (CT) is somewhat useful, but not all tumors are readily apparent on CT, especially if they do not enhance with the administration of contrast medium. Therefore, MRI is highly recommended for brain tumor evaluation. MRI is relatively good at identifying the tumor type (meningioma versus glioma, for example) and has some capability to grade tumors. Cerebrospinal fluid (CSF) taps are rarely useful in diagnosing brain tumors, but are useful in cases in which the MRI appearance of a lesion is consistent with either a neoplasm or meningoencephalitis of unknown etiology. Ultimately, Champ’s diagnosis requires referral to a clinic with MRI capabilities. Such referral may be declined for a variety of reasons. MRI is still an expensive diagnostic tool and may not be financially feasible for many clients. Referral centers may be long distances away and coordinating days off for travel may be too challenging. Others may decline referral if they are not planning on pursuing additional treatment for whatever the MRI discloses. Although MRI confirmation of a brain tumor is ideal, there is an alternative option for presumptive brain tumor diagnosis: “Time as a diagnostic test.” Dogs with brain tumors will show progressive signs of their disease over time. In the case of dogs with a new onset of seizures, but normal neurological exams, time as a diagnostic test can strongly distinguish between idiopathic epilepsy and intracranial causes of brain tumors. As brain tumors grow, dogs will start to show neurological deficits referable to the region of the brain affected by the tumor. The rate of progression depends on how quickly the tumor grows. Dogs with tumors in the prosencephalon will start to show gradual mentation changes. In general, they become less alert. They may also stare at walls, get stuck in corners, and forget which side of a door opens. They will start to pace propulsively in one direction. Their seizures may worsen in frequency and duration. Seizure phenotype can progress in dogs with epilepsy, but will not be accompanied by the development and progression of neurological dysfunction. Likewise, another cause of seizures and neurological abnormalities in dogs, strokes, will not lead to progressive dysfunction. Rather, dogs with strokes will show gradual improvement in their neurological status over a period of days to weeks. Thus, in patients for which referral and imaging is not feasible, monitoring their progress over time is a reasonable path to a presumptive brain tumor diagnosis. What are the treatment options for dogs with primary brain tumors? Broadly, treatment options consist of definitive care and palliative care. Definitive care consists of tumor-targeted therapies, including surgical debulking or resection, radiation therapy, and in some cases, chemotherapy. Although several treatment modalities do successfully prolong survival times for dogs with brain tumors (Hu et al. 2015), many clients decline these options. When definitive treatment is not an option, for whatever reason, this leaves two options to present to the client: palliative care and euthanasia. After finishing your reading, you return to the exam room to discuss your assessment with Champ’s owner. She asks how a brain tumor could be diagnosed, and you offer a referral to the nearest specialty clinic. You briefly go over expected outcomes with definitive treatment and the expected costs. You have the information from your colleague, who is managing a patient who underwent radiation therapy for a meningioma. Champ’s owner says she is unable to pursue the referral due to cost constraints. She wants to know how she can care for Champ, what his disease progression will look like, and if she will need to euthanize him or if he will die on his own. Dogs that are having seizures, regardless of the underlying cause, should be started on an anticonvulsant when at least one of the following criteria is observed (Podell et al. 2016): 1) An identifiable structural lesion is present 2) Status epilepticus or three or more seizures in 24 hours 3) Two or more seizures in a six month period 4) Extended or severe post-ictal periods In Champ’s case, his abnormal neurological exam indicates a structural brain abnormality is present, and will continue to cause seizures. Thus, a major part of Champ’s palliative care plan is starting him on an anticonvulsant. Currently, there are four mainstay anticonvulsants available in the United States: phenobarbital, potassium bromide, zonisamide, and levetiracetam. A comprehensive summary of their efficacy and safety is available in Podell et al. 2016. Anticonvulsants are effective at controlling seizures in dogs with brain tumors for a variable period of time, depending on the size of the tumor and the rate of tumor growth. The other mainstay of palliative care treatment for dogs with presumptive or MRI-confirmed brain tumors is corticosteroid therapy, generally consisting of prednisone or prednisolone. These medications reduce peritumoral edema and inflammation, and they may help to slow tumor growth. There are no established guidelines regarding the type of corticosteroid, dose, and frequency. The author’s recommendation is to start with 0.5-1mg/kg/day for five to seven days, then taper to the lowest effective dose indefinitely. If the patient’s status deteriorates with dose reduction, then a higher dose should be resumed. Clients should be advised of the main side effects of corticosteroids, including polyuria, polydipsia, polyphagia, panting, and occasionally agitation or lethargy. Many clients become concerned about effects from chronic steroid use, such as endocrinopathies. Ultimately, most dogs with brain tumors do not survive long enough to be at risk for such effects. How long do dogs with brain tumors survive if treated with palliative care? There are limited data regarding survival outcomes for dogs treated palliatively. It is challenging to determine survival times without a definitive diagnosis. Even when tumors are diagnosed via MRI, studies vary in how they report survival times. Some report from the onset of clinical signs. Others report from the time of imaging-based diagnosis. Yet, in both cases, tumors have been growing for an indeterminate weeks to months prior to diagnosis. Without a diagnosis, it is also difficult to prognosticate based on tumor type, but in general, an educated guess regarding tumor type is possible in many dog breeds. Based on a retrospective study, tumor type may not matter as much as tumor location: dogs with rostrotentorial tumors lived on average 180 days from the time of diagnosis, whereas those with tumors affecting the midbrain, pons, or medulla, lived on average 28 days (Rossmeisl et al 2012). Recently, a small study on dogs with gliomas disclosed a median survival time of 26 days (Jose-Lopez et al. 2021) when treated palliatively. Since Champ is a boxer, his presumptive tumor is most likely of glial origin. Given the heterogeneity of these tumors between patients as well as the challenges associated with measuring survival times, providing Champ’s owner with a definitive answer regarding survival time will ultimately be an educated guess. Even though the median survival time was only 26 days in Jose-Lopez et al., this is a population statistic, not an individual one. Some dogs live only a few days following their diagnosis, while others live several months following their diagnosis. Therefore, the author’s recommendation regarding survival time projections for individuals is to explain each patient and each tumor is different, and gauging quality of life markers is more appropriate than assigning an expected survival time. Clients should be informed about what to expect as the tumor progresses so they can make as informed a decision as possible regarding criteria for euthanasia. Neurological signs will progress over time and seizures may become more severe, prolonged, and frequent. Seizures may progress to status epilepticus and death. Just like each tumor is different, every client is different regarding what they consider a reasonable quality of life for their pet. Some may elect to euthanize their pet upon learning of the presumptive diagnosis if they want to avoid any potential suffering. Others may lose perspective and need gentle guidance when objectively, euthanasia is the best option. Conclusion Brain tumors are relatively common in dogs, and are becoming more common as brachycephalic dog breeds continue to rise in popularity. Thorough history acquisition and neurological examinations can help in the presumptive diagnosis of a brain tumor. Palliative care does provide some time for acceptable quality of life for many dogs, with a wide range in survival times. As for Champ, following his presumptive diagnosis, he responded favorably to prednisone and anticonvulsant therapy for 10 weeks. Then, his mentation declined and his seizures started to occur every two to three days. His owners elected to have him euthanized when he was no longer interacting with them. Susan A. Arnold, DVM, DACVIM (Neurology) is an assistant professor of neurology and neurosurgery at the University of Minnesota College of Veterinary Medicine. She is boarded within the American College of Veterinary Internal Medicine (Neurology). In her role, Dr. Arnold practices neurology and neurosurgery, trains interns and residents, and teaches veterinary medical students in both didactic and clinical settings. References Podell M, Volk HA, Berendt M, et al. 2015 ACVIM Small Animal Consensus Statement on Seizure Management in Dogs. J Vet Intern Med. 2016 Mar-Apr;30 (2):477-90. doi: 10.1111/jvim.13841. Epub 2016 Feb 22. PMID: 26899355; PMCID: PMC4913615. Loncarica T, Balducci F and Bernardini M. Prevalence of idiopathic epilepsy and structural epilepsy in 74 Boxer dogs in a referral hospital. Front. Vet. Sci. 2022; 9:956648. doi: 10.3389/fvets.2022.956648. Hu H, Barker A, Harcourt-Brown T, Jeffery N. Systematic Review of Brain Tumor Treatment in Dogs. J Vet Intern Med.2015 Nov-Dec;29(6):1456-63. doi: 10.1111/jvim.13617. Epub 2015 Sep 16. PMID: 26375164; PMCID: PMC4895648. José-López R, Gutierrez-Quintana R, de la Fuente C, et al. Clinical features, diagnosis, and survival analysis of dogs with glioma. J Vet Intern Med. 2021;35(4):1902–17. https://doi.org/10.1111/jvim.16199. Mallol C, Gutierrez-Quintana R, Hammond G, Schweizer-Gorgas D, De Decker S, Novellas R, Espada Y, Oevermann A, Ortega M, Parry A, Coelho AM, Gonçalves R, Stalin C, Brocal J. MRI features of canine hemangiosarcoma affecting the central nervous system. Vet Radiol Ultrasound. 2022 Mar;63(2):185-196. doi: 10.1111/vru.13041. Epub 2021 Dec 6. PMID: 34873768. Miller, A. D., Miller, C. R., Rossmeisl, J. H. (2019). Canine primary intracranial cancer: a clinicopathologic and comparative review of glioma, meningioma, and choroid plexus tumors. Frontiers in oncology, 9, 1151. Rossmeisl JH Jr, Jones JC, Zimmerman KL, Robertson JL. Survival time following hospital discharge in dogs with palliatively treated primary brain tumors. J Am Vet Med Assoc. 2013 Jan 15;242(2):193-8. doi: 10.2460/javma.242.2.193. PMID: 23276095.

Cookie	Duration	Description
cookielawinfo-checkbox-analytics	11 months	This cookie is set by GDPR Cookie Consent plugin. The cookie is used to store the user consent for the cookies in the category "Analytics".
cookielawinfo-checkbox-functional	11 months	The cookie is set by GDPR cookie consent to record the user consent for the cookies in the category "Functional".
cookielawinfo-checkbox-necessary	11 months	This cookie is set by GDPR Cookie Consent plugin. The cookies is used to store the user consent for the cookies in the category "Necessary".
cookielawinfo-checkbox-others	11 months	This cookie is set by GDPR Cookie Consent plugin. The cookie is used to store the user consent for the cookies in the category "Other.
cookielawinfo-checkbox-performance	11 months	This cookie is set by GDPR Cookie Consent plugin. The cookie is used to store the user consent for the cookies in the category "Performance".
JSESSIONID	session	The JSESSIONID cookie is used by New Relic to store a session identifier so that New Relic can monitor session counts for an application.
viewed_cookie_policy	11 months	The cookie is set by the GDPR Cookie Consent plugin and is used to store whether or not user has consented to the use of cookies. It does not store any personal data.

Cookie	Duration	Description
vuid	2 years	Vimeo installs this cookie to collect tracking information by setting a unique ID to embed videos to the website.
_ga	2 years	The _ga cookie, installed by Google Analytics, calculates visitor, session and campaign data and also keeps track of site usage for the site's analytics report. The cookie stores information anonymously and assigns a randomly generated number to recognize unique visitors.
_gat	1 minute	This cookie is installed by Google Universal Analytics to restrain request rate and thus limit the collection of data on high traffic sites.
_gat_UA-	1 minute	A variation of the _gat cookie set by Google Analytics and Google Tag Manager to allow website owners to track visitor behaviour and measure site performance. The pattern element in the name contains the unique identity number of the account or website it relates to.
_gid	1 day	Installed by Google Analytics, _gid cookie stores information on how visitors use a website, while also creating an analytics report of the website's performance. Some of the data that are collected include the number of visitors, their source, and the pages they visit anonymously.
__gads	1 year 24 days	The __gads cookie, set by Google, is stored under DoubleClick domain and tracks the number of times users see an advert, measures the success of the campaign and calculates its revenue. This cookie can only be read from the domain they are set on and will not track any data while browsing through other sites.

Cookie	Duration	Description
ADV_u_id	3 months 8 days	Unique customer identifier used to track unique ad views and interactions with some ads.
anj	3 months	AppNexus sets the anj cookie that contains data stating whether a cookie ID is synced with partners.
fr	3 months	Facebook sets this cookie to show relevant advertisements to users by tracking user behaviour across the web, on sites that have Facebook pixel or Facebook social plugin.
IDE	1 year 24 days	Google DoubleClick IDE cookies are used to store information about how the user uses the website to present them with relevant ads and according to the user profile.
loc	never	AddThis sets this geolocation cookie to help understand the location of users who share the information.
OAGEO	session	OpenX sets this cookie to avoid the repeated display of the same ad.
OAID	1 year	Cookie set to record whether the user has opted out of the collection of information by the AdsWizz Service Cookies.
test_cookie	15 minutes	The test_cookie is set by doubleclick.net and is used to determine if the user's browser supports cookies.
uuid2	3 months	The uuid2 cookie is set by AppNexus and records information that helps in differentiating between devices and browsers. This information is used to pick out ads delivered by the platform and assess the ad performance and its attribute payment.
_fbp	3 months	This cookie is set by Facebook to display advertisements when either on Facebook or on a digital platform powered by Facebook advertising, after visiting the website.

When is a canine seizure a brain tumor?

A look at Champ’s case study; from diagnosis to palliative care options

Membership Required