Vestibular Syndrome Due to a Choroid Plexus Papilloma in a Ferret

Introduction

Dysfunction of the vestibular system is commonly recognized by signs such as head tilt, leaning, circling, and rolling. Nystagmus (either horizontal, rotary, vertical, or positional) can also be seen.^1,2 Depending on the location of the lesion, vestibular disease can be classified either as peripheral (resulting from lesions to the vestibular receptors in the membranous labyrinth or vestibulocochlear nerve deficits) or central (lesions in the vestibular nuclei, brain stem, or flocculonodular lobe of the cerebellum in the central nervous system [CNS]).^1,2 Both types can usually be distinguished by the presence of specific signs. In peripheral vestibular disease, Horner’s syndrome, horizontal or rotary nystagmus, and/or facial paralysis are often noted. In central vestibular disease, however, more severe signs may be seen with regard to the locomotor system. Such signs often consist of ataxia combined with hypermetria and/or hemiparesis with proprioceptive deficits. In addition, cranial nerve (V, VI, and VII) deficits, such as paralysis of facial and masticatory muscles and loss of facial sensation, can be present. Nystagmus, if present, can be horizontal, rotary, vertical, or positional.^1,2 Severity of signs depend mainly on the cause, extent, and rate of onset of the vestibular disease.

Causes of vestibular dysfunction, as recognized in animals, can be congenital, traumatic, vascular, inflammatory, toxic, nutritional, neoplastic, or idiopathic.^1,2 In ferrets, vestibular ataxia has been reported to occur as a result of intoxications, infections (e.g., Aleutian disease, canine distemper, rabies, Toxoplasma gondii), neoplasia, or trauma.^3-7 Hypoglycemia secondary to insulinoma is considered to be the principal differential diagnosis in ferrets displaying ataxia of the rear limbs, followed by trauma, neoplasia, and infectious diseases within the spinal cord, respectively.^6,7 Distinction between these different types of ataxia is important for localization of the problem and determination of the cause.⁷

This case report describes the onset of central vestibular disease resulting from the presence of a choroid plexus tumor of the fourth ventricle in a ferret.

Case Report

A 6-year-old, neutered male ferret (Mustela putorius furo) was referred to the Division of Avian and Exotic Animal Practice of the Utrecht University with a 2-month history of progressive neurological complaints. Head tilt, circling and falling to the right, incoordination while walking, and progressive weakness in the hind legs were reported. Appetite and drinking were considered normal, although the ferret had lost weight (approximately 140 grams) over the last 3 months and currently weighed 740 grams. The ferret was vaccinated against canine distemper virus and had been recently treated for ear mite infestation with ivermectin (Ivomec)^a by the referring veterinarian.

On initial presentation, the ferret was bright, alert, and responsive with no abnormalities of breathing, pulse, temperature, or mucous membranes. Neurological examination revealed a head tilt to the right and ataxia of the head, body, and limbs. Aright-sided hemiparesis was noted. Furthermore, proprioception was absent on the right side, while postural reactions on the left side were present.

Because the ferret initially was presented with weakness of the hind limbs, differential diagnoses included insulinoma (and other metabolic disturbances), bacterial or viral meningoencephalitis, intracranial neoplasia, vascular incidents, trauma, intoxication, and thiamine deficiency. The presence of a right-sided head tilt and ataxia, combined with hemiparesis and proprioceptive deficits on the right side (found on subsequent examinations), were more consistent with central vestibular disease than with metabolic abnormalities and secondary weakness and ataxia.

To exclude insulinoma, blood glucose was measured and considered to be within normal limits (4.3 mmol/L; reference range 4.4 to 6.7 mmol/L). Because a lesion in the CNS was thought to be the most likely cause of the vestibular ataxia, diagnostic imaging was considered the most important part of additional testing. A computed tomographic (CT) examination of the skull, using a third-generation spiral CT scanner (Philips TomoScan),^b was performed with the ferret in ventral recumbency and anesthetized with 2% isoflurane (IsoFlo).^c Consecutive transverse slices (2 mm) were made through the entire skull before and after intravenous administration of 1 mL of ionic iodinated contrast medium (Telebrix 380, containing 380 mg iodine per mL).^d Transverse slices (1 mm) were reconstructed. Multiplanar reconstructions were made in sagittal and dorsal planes.

Precontrast images showed a slightly hyperattenuating region on the right side of the cerebellomedullary angle, just medial to the right tympanic bulla [Figure 1A]. A definitive conclusion of an abnormality could not be drawn because of the presence of beam-hardening artifacts that resulted from removal of low-energy photons from the polychromatic spectrum used in CT imaging. The dense petrous temporal bone surrounding the brain causes absorption of these low-energy beams, while high-energy beams pass through, resulting in decreased density of the structures behind the bone and creation of artifactual linear areas of hypodensity in the adjacent brain. After the contrast medium was administered, irregular enhancement of the slightly hyperattenuating region in the cerebellomedullary angle, at the ventral right side of the brain stem, was visible [Figures 1B, 2]. This region, which measured 8 (length) × 9 (width) × 8 (height) mm, appeared to be well defined with a rounded appearance, and it could clearly be distinguished from surrounding brain tissue. These findings were considered to be compatible with either an inflammatory or neoplastic process.

Because of the small size and location of the mass, surgery was not considered to be a viable option. Palliative treatment was started with a single dose of dexamethasone (Dexadreson^e 0.5 mg/kg subcutaneously), followed by prednisolone suspension (Prednisolone 5^f 1 mg/kg q 24 hours orally). After 2 weeks of treatment, no improvement was seen. Because of the poor prognosis, the ferret was euthanized and necropsied.

Macroscopically, no abnormalities were found on the outer surfaces of the brain, skull, and ears. The brain was removed and cut into transverse sections, which revealed a well-defined, grayish, granular mass of approximately 1 × 1 × 2 cm in the right ventrocranial area of the cerebellum, occupying most of the space in the fourth ventricle [Figures 3A, 3B]. The mass likely originated in the fourth ventricle and extended into the other ventricles. Dilatation of all ventricles (third, fourth, and lateral) was indicative of hydrocephalus.

Microscopically, the mass consisted of a branching arboriform proliferation of fibrovascular stroma covered with a single layer of predominantly cuboidal epithelium [Figures 4, 5]. The epithelial cells were uniform in size and shape. The mitotic index was judged to be low, with five mitoses observed per 10 high-power fields. No infiltration was seen in surrounding tissue. These findings are consistent with a choroid plexus papilloma of the fourth ventricle.

Discussion

To the authors’ knowledge, this is the first report describing the presence of a choroid plexus papilloma in a ferret. Intracranial neoplasms have previously been described in ferrets, although the incidence appears to be low compared with that in other species.^8-10 In one report, five brain tumors were detected among a total of 1525 neoplasms in ferrets, corresponding to a prevalence of 0.33%.¹¹ Sleeman and others (1996) were the first to report the presence of a primary tumor in the CNS of a 4-year-old male ferret; the tumor was later histologically confirmed to be a granular cell tumor (also called myoblastoma).⁵ This ferret initially showed a right head tilt, circling to the right, and ataxia, which progressed to seizure activity.

Other primary intracranial neoplasms that have been reported are pituitary gland tumors (n=2), astrocytomas (n=3), meningiomas (n=2), a glia cell tumor, and a primitive neuroepithelial cell tumor.^10-12

Choroid plexus tumors are encountered only rarely in animals and humans.^13-18 They have been described in cats, horses, cows, and more frequently in dogs.^13,15,18-24 In the latter species, they are mostly found in middle-aged dogs (mean age 6 years; range 2 to 13 years) and comprise approximately 4% to 9% of all brain tumors.^{18,19,21,22,24} Choroid plexus tumors can be subdivided into choroid plexus papillomas and carcinomas (also sometimes referred to as anaplastic choroid plexus papillomas).^18,24 Approximately 80% of choroid plexus tumors are benign, slow-growing papillomas, while the other 20% are biologically more aggressive tumors.^16,17

Choroid plexus tumors can develop in the lateral, third, or fourth ventricle, with the fourth ventricle being the pre-dominant location in adult humans and dogs (40% and 60%, respectively).¹⁸ In children, these tumors are usually found in the lateral ventricle (50% of cases).^{13,14,16,17,22,25} The fourth ventricle was also the site of the choroid plexus papilloma in this ferret.

The two most important differential diagnoses for a choroid plexus papilloma are choroid plexus carcinoma and ependymoma. The choroid plexus carcinoma is distinguished from the papilloma by the presence of frequent mitotic activity, accompanied by cellular pleomorphism, nuclear atypia, local invasion into adjacent brain tissue, and/or metastatic behavior within the cerebrospinal fluid (CSF) pathway.^17,18,24 Ependymomas are differentiated from choroid plexus papillomas by the presence of ependymal rosettes (linear tubules of cuboidal cells), perivascular pseudorosettes (lining of glial cells around blood vessels), and a fibrillated, noncollagenous background.^17,22

The clinical signs shown by this ferret were consistent with those described in other species (i.e., hemiparesis, ataxia, and loss of equilibrium).^13,14,23,26 Hydrocephalus, which was seen at the postmortem examination, is also regularly described in other animals with choroid plexus papilloma. ^17,27 The hydrocephalus may develop as a result of either obstructed drainage or increased production of CSF by the tumor cells.^13,17 The presence of hydrocephalus was not detected on the CT images of the skull, which were made 3 weeks before the ferret was euthanized. Either the resolution detail of the CT image was too limited for correct interpretation, or the hydrocephalus had developed in the 3 weeks between CT imaging and euthanasia.

Analysis of CSF, electroencephalographic (EEG) examination, ultrasonography, CT scans, and magnetic resonance imaging have all been reported as techniques aiding in the diagnosis of intracranial neoplasms.^20,26,28,29 Diagnosing the origin and type of the neoplasm, however, is not possible with any of these techniques.^26,28,30 Ultrasonography or CTguided fine-needle aspirates have proven to be valuable tools in diagnosing the type of tumor in vivo, but excisional biopsy is still considered the primary method of diagnosis, because material can be obtained for full histopathological examination (i.e., not limited to cytology).¹³ Because of the size and location of the tumor in this ferret, the authors decided an antemortem diagnosis was not feasible to pursue.

In humans, choroid plexus papillomas are surgically resected, and the overall prognosis is excellent.^17,27 No clear data are available for defining the role of surgery, radiation therapy, or chemotherapy in animals. If the tumor is accessible, surgery would be considered the treatment of choice, although surgery is often hindered because the tissue is heavily vascularized.^13,31 In the authors’ case, size of the tumor in combination with its relative inaccessibility were the limiting factors and precluded surgery as an option.

Conclusion

This case report describes the occurrence of central vestibular syndrome, caused by an intracranial mass, in a ferret. Contrast-enhanced CT imaging facilitated antemortem diagnosis of the intracranial neoplasm. Postmortem examination, including histopathology, revealed the tumor to be a choroid plexus papilloma originating from the fourth ventricle. To the authors’ knowledge, choroid plexus papillomas have not been reported previously in ferrets. However, they should be considered in the differential diagnosis of ferrets displaying central neurological signs. This case report further demonstrates that contrast-enhanced CT imaging can be of great value in identifying intracranial masses in ferrets, and it can potentially be used for similar purposes in other small species. Although CT-guided biopsies of intracranial masses have been performed with success in dogs and humans,³² antemortem diagnosis was not pursued in this ferret because of the small size and location of the tumor.