Tips to diagnose and treat feline meningiomas

Because feline meningiomas are slow growing, noninvasive, and generally do not metastasize, surgical resection is considered the optimal definitive treatment route. Photo: Bigstock/Kuran Feline meningiomas are the most common primary brain tumor in cats.1 These relatively slow-growing tumors originate from the arachnoid layer of the meninges that surround the brain and cause compression and subsequent dysfunction of the surrounding brain tissue. There are several other differential diagnoses to consider when presented with a cat suspected to have a meningioma. There are a variety of treatment options available for feline meningiomas. This article provides details about feline meningiomas in the framework of a case. Case introduction Zephyr is a 16-year-old neutered male domestic shorthaired cat that was presented to his primary veterinarian for progressive lethargy. History In the weeks leading up to this visit, Zephyr’s owners have observed an overall decrease in his interest in his toys and in interacting with the family. Zephyr is normally a very social cat but has taken to spending most of his time walking around the house, seemingly in a trance-like state. His owners believe it has gotten slightly worse since they first noticed the change. Zephyr has a history of hyperthyroidism that was treated with radioactive iodine successfully about eight years prior. He is an indoor-only cat, although he does have supervised outdoor time in their fenced backyard. He is current on his vaccinations, and eats a commercial, cooked kibble food formulated for cats. Takeaways: As a geriatric cat, there are many conditions that can lead to a sudden and gradually progressive deterioration in mentation. When presented with a geriatric cat with a history like Zephyr’s, consider a broad variety of both extracranial and intracranial causes. Extracranial conditions refer to those outside the brain that can have secondary impacts on brain function. In an aged cat, some initial considerations would include an electrolyte abnormality, particularly hypokalemia (which can make patients appear generally weak) anemia, and liver disease with secondary hepatic encephalopathy. Physical examination Zephyr was overtly bright, alert, and responsive on his examination. He is generally a vocal cat during examinations, and he was especially vocal on this examination. His vitals were normal. He weighed 3.8 kg, which was decreased from his last recorded weight of 4.1 kg from two months prior. He had a grade II/VI parasternal systolic murmur with a normal rate and rhythm. His lungs ausculted normally. His abdomen was soft on palpation, and no free fluid, masses, or organomegaly were appreciated. His oral cavity was normal other than diffuse tartar on all premolars and molars. He appeared to be slightly dehydrated. Zephyr was placed on the floor of the examination room while the findings were discussed. It became evident Zephyr consistently paced around the room in counterclockwise circles. When questioned, his owner mentioned they had observed similar pacing at home over the past several weeks. They also said he had been knuckling his right front paw at times when he was eating at his food bowl. Based on this observation and the additional information, a neurologic exam was subsequently performed. Zephyr’s neurologic examination Mentation: Although originally considered to be bright, alert, and responsive, with further evaluation, he was less interactive than he usually is during his examinations. He also hissed during his exam, which is very abnormal for him. Gait and posture: Zephyr walked with a normal gait, meaning that he had no observable paresis, ataxia, or lameness. However, he consistently walked in counterclockwise (leftward) circles. His posture was normal. Muscle mass and tone: Normal in all four limbs. Postural reactions: Zephyr had severely delayed postural reactions in his right thoracic and pelvic limbs. His postural reactions were normal in his left limbs. Spinal reflexes: All of his spinal reflexes were normal. Cranial nerves: Zephyr lacked a menace response in his right eye. The rest of his cranial nerves were normal. Based on his examination findings, where would you localize Zephyr’s neurologic dysfunction? Neurolocalization 1) Mentation: Zephyr’s decreased mentation by default points to an issue in his brain. Both the prosencephalon (comprised of the cerebrum and the thalamus, along with all surrounding diencephalic structures) and the brainstem (functionally comprised of the midbrain, pons, and medulla) can lead to a decrease in the level of consciousness. 2) Postural reactions and gait evaluation: Postural reaction deficits can be observed with a lesion in both the prosencephalon and the brainstem. However, a key distinguishing feature in a patient with postural reaction deficits is whether or not these postural reaction deficits are associated with gait abnormalities. Patients with a lesion in the prosencephalon will have a normal gait, meaning they have no observable paresis or ataxia as they are walking around the room. Contrastingly, patients with a lesion in the brainstem often have an abnormal gait, characterized by a combination of paresis and ataxia. As Zephyr is not showing any gait abnormalities while he walks around, a lesion in the brainstem is considered unlikely. This means that the postural reaction deficits are due to a problem in the prosencephalon. This is further reinforced by Zephyr’s consistent circling to the left. Patients with prosencephalic lesions often demonstrate “propulsive circling,” in which they walk consistently in one direction, even when it is more convenient to walk in the other direction. 3) Menace response: Zephyr’s absent menace response in his right eye points to an issue in at least one of the neuroanatomic components involved in the menace response. These include the ipsilateral retina, cranial nerve II, optic chiasm, contralateral optic tract, contralateral cerebral cortex, and ipsilateral cranial nerve VII. The results of other cranial nerve tests can help to rule out some of these components as the cause of Zephyr’s right menace deficit. His pupillary light reflexes were normal. This reflex involves cranial nerves II and III. Therefore, the retina, cranial nerve II, the optic chiasm, and the contralateral optic tract are ruled out as a possible cause of Zephyr’s menace deficit. Zephyr’s palpebral reflexes were normal. This reflex involves cranial nerves V and VII. Therefore, CN VII is not the cause of Zephyr’s right menace deficit. By process of elimination, this means that Zephyr’s right menace deficit is due to a lesion in his prosencephalon. The combination of Zephyr’s decreased mentation, right-sided postural reaction deficits, right-sided menace deficit, and circling to the left are consistent with a lesion in the left prosencephalon. The left prosencephalon receives and processes all information from the right side of a patient. This includes the right visual field, and the proprioceptive information from the right limbs. Because of the lesion in the left prosencephalon, visual information from the right visual field is not processed. This explains Zephyr’s right-sided menace deficit. It also explains why he is walking in propulsive circles to the left. This seeming lack of awareness of the right side of the patient’s surroundings is called hemi-inattention or hemi-neglect. Because the visual information from the right side is unable to be processed by the left prosencephalon, and the patient only receives information from the left visual field, Zephyr walks in propulsive circles to the left, as it is the only visual field accessible for him to process. The right-sided proprioceptive deficits occur because kinesthesia is processed by the contralateral prosencephalon. The lesion in Zephyr’s left prosencephalon, therefore, explains his right-sided postural reaction deficits. Differential diagnoses There are several important differential diagnoses to consider for a cat with a progressive, unilateral prosencephalic lesion. First, causes of bilateral prosencephalic disease can likely be ruled out. These include degenerative brain diseases, such as storage disorders, metabolic diseases, such as hypoglycemia, nutritional diseases, such as thiamine deficiency, and toxins, such as bromethalin toxicity. All these processes would not affect one side of the brain exclusively. Likewise, diseases of young animals, such as congenital hydrocephalus, are very unlikely in aged patients. A vascular cause, such as a stroke, is unlikely for this cat because his signs have occurred gradually and progressively, rather than acutely and statically. Noninfectious, inflammatory diseases, such as immune-mediated diseases, are generally uncommon in cats and would not be expected in such an aged animal. After ruling out these broad differential diagnoses categories, the remaining possibilities include infectious causes and neoplastic causes. A variety of infectious organisms, including viral, bacterial, protozoal, fungal, and parasitic, can lead to lateralized prosencephalic disease in cats. Various tumors, both primary and metastatic, can also lead to the same signs. Diagnosing feline meningioma Ultimately, the neurologic exam will help the practitioner in localizing the lesion, and various factors of an individual case can help with prioritizing differential diagnoses for that particular lesion localization in that particular patient. The most sensitive tests to distinguish between differentials for a patient with a lateralized prosencephalic lesion is a combination of a magnetic resonance imaging (MRI) series of the brain and potentially a cerebrospinal fluid (CSF) analysis. Prior to performing these diagnostic tests, which require general anesthesia, patients should be assessed for systemic issues that could pose an increased anesthetic risk, including cardiac, respiratory, renal, and hepatic disease. Thoracic radiographs are also a good screening test to ensure that a patient does not have systemic evidence of neoplasia or infection. Figure 1. MRI images of Zephyr’s meningioma. A and C are T2W images. B and D are post-contrast images. On all views, the mass is well-defined from surrounding brain tissue, exhibits a broad base, and causes severe deviation and compression of the adjacent parenchyma. The mass is strongly, uniformly contrast enhancing. The yellow arrows point to regions of contrast enhancement at the periphery of the mass, referred to as a “dural tail.” Courtesy Dr. Susan Arnold Zephyr’s owners elected to proceed with a complete blood count and blood chemistry panel, which did not disclose any abnormalities that would preclude anesthesia. He underwent a brain MRI. A cerebrospinal fluid tap was not performed because the MRI provided strong support for the presumed diagnosis of a feline meningioma (Figure 1). Feline meningiomas are generally readily distinguishable on MRI from other differentials, such as infections. These masses are discrete and well-demarcated, and originate from outside of the brain and push inward, causing deviation and compression of the adjacent brain tissue. Since these tumors originate from the meninges, they tend to be broad-based and can have a classic feature called a dural tail. A dural tail is an area of thickened meninges on the periphery of the tumor. These tumors are generally strongly contrast-enhancing, as well. Definitive diagnosis of a feline meningioma requires histopathologic evaluation (Figure 2). Meningiomas can be graded into histopathological subtypes of grades 1, 2, and 3.2 They can also be graded based on morphological features into fibrous, transitional, meningothelial, atypical, and anaplastic. Most feline meningiomas are grade 1 tumors, growing slowly over a period of many months, and the most common morphological type is transitional, followed by fibrous.3 Feline meningiomas can also develop characteristic “cholesterol clefts” that distinguish them from other tumor types.3 Figure 2. Histopathologic image of a feline meningioma: Typical appearance of a transitional subtype meningioma. Courtesy Ariel de Aguiar, University of Minnesota Treatment options Broadly, there are two categories of treatment for brain tumors: palliative care and definitive care. These options were discussed with Zephyr’s owners. Palliative care consists of providing anti-inflammatory doses of prednisolone to reduce peritumoral edema. Survival time is variable and depends on tumor location, size, and response to prednisolone, but generally is less than a few months.4 Definitive care consists of treatment directly targeting the tumor. Because feline meningiomas are slow growing, noninvasive, and generally do not metastasize, surgical resection is considered the optimal definitive treatment route. For most cats, surgical resection is considered “curative.” The tumor takes such a long time to regrow that even if there is residual tumor following resection, most cats will succumb to unrelated diseases before their tumor becomes problematic again. However, surgery does pose a higher mortality risk from surgical complications, including hemorrhage, damage to neuroparenchyma, and infection, compared to other treatment approaches. However, surgical resection is not always possible for feline meningiomas. Tumors may not be in locations safely accessible for surgery. In these cases, radiation therapy is another reasonable treatment option for feline meningiomas. Progression-free survival of roughly 500 days has been reported in cats.5 There is also a case report of a non-resectable feline meningioma that was treated with a combination of prednisolone and hydroxyurea, a medication that induces tumor cell apoptosis, yielding a survival time of over 400 days in the patient.6 After discussing these various options, Zephyr’s owners elected to proceed with surgical resection. In the days leading up to his surgery, he was placed on an anti-inflammatory dose of prednisolone, which minorly improved his signs. Surgery consisted of a rostrotentorial craniectomy in which a rectangular piece of bone covering the tumor was drilled away and removed, giving access to the tumor. The tumor tissue was readily identified compared to normal brain because the tumor was dark pink and lacked the typical sulci-gyri architecture of the surrounding light pink brain tissue. Case outcome The tumor was removed in large pieces. Zephyr did well during surgery and recovered uneventfully. After spending a night in the intensive care unit without any issues, Zephyr was evaluated the morning after surgery. His mentation was mildly improved compared to prior to surgery. He ate readily. He was discharged to his family later that afternoon, on a tapering course of prednisolone over the following weeks. Three weeks after surgery, Zephyr’s owners provided a video demonstrating Zephyr’s overall condition had markedly improved. He was playing with cat toys he had not touched in years. He was interactive and no longer aimlessly pacing. He lived another three years without evidence of tumor recurrence before succumbing to unrelated health issues. Conclusions Meningiomas are the most common primary intracranial brain tumor in cats. They tend to affect older cats and lead to slowly progressive signs that may rapidly progress in later stages. Other conditions can cause similar signs in older cats and diagnosis requires imaging, preferably in the form of a brain MRI. Because these tumors are low grade, surgical resection can provide years of good quality of life for affected cats, and there are other treatment options available when surgery is unadvised or not desired. 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 Cameron S, Rishniw M, Miller AD, et al. Characteristics and Survival of 121 Cats Undergoing Excision of Intracranial Meningiomas (1994-2011). Vet Surg 2015;44(6):772-6, doi:10.1111/vsu.12340. Meuten D. J.2017. Tumors of the nervous system. pp. 834–891. Tumors in Domestic Animals, 5th ed. (Higgins, R. J. ed.), Wiley-Blackwell, Hoboken. Saito R, Chambers JK, Kishimoto TE, Uchida K. Pathological and immunohistochemical features of 45 cases of feline meningioma. J Vet Med Sci. 2021 Aug 6;83(8):1219-1224. doi: 10.1292/jvms.21-0258. Epub 2021 Jun 23. PMID: 34162785; PMCID: PMC8437717. Troxel MT, Vite CH, Van Winkle TJ, et al. Feline intracranial neoplasia: retrospective review of 160 cases (1985-2001) J Vet Intern Med. 2003;17(6):850–859. Körner M, Roos M, Meier VS, et al. Radiation therapy for intracranial tumours in cats with neurological signs. J Feline Med Surg. 2019 Aug;21(8):765-771. doi: 10.1177/1098612X18801032. Epub 2018 Oct 19. PMID: 30339060; PMCID: PMC10814305. Yun T, Koo Y, Kim H, et al. Case Report: Long-Term Chemotherapy With Hydroxyurea and Prednisolone in a Cat With a Meningioma: Correlation of FDG Uptake and Tumor Grade Assessed by Histopathology and Expression of Ki-67 and p53. Front Vet Sci. 2021 Jan 26;8:576839. doi: 10.3389/fvets.2021.576839. PMID: 33575281; PMCID: PMC7870713.

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Tips to diagnose and treat feline meningiomas

A case study of Zephyr on the most common type of feline primary intracranial brain tumor

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