Topics in Companion An Med 43 (2021) 100509 Case Report Paradoxical Vestibular Syndrome Caused by a Presumptive Cerebellar Infarction in a Rabbit Rafael García, DVMa, Sonia An~ or, DVM, PhD, Dip ACVIM (Neurology), Dip ECVNa,b,*, Cristian de la Fuente, DVM, PhD, Dip ECVNa,b, Rosa Novellas, DVM, PhD, Dip ECVDIb,c, Vicente Soler, DVMd, Jaume Martorell, DVM, PhD, Dip ECZMb,d Keywords: A 6-year-old, female spayed rabbit (Oryctolagus cuniculus) presented with right paradoxical vestibular signs. paradoxical vestibular syndrome Magnetic resonance imaging was performed and findings were consistent with an ischemic infarct of the cer- rabbit ebellum. The patient improved gradually and was free of clinical signs at the time this article was written. To cerebrovascular accident the authors’ knowledge this is the first case report of a paradoxical vestibular syndrome in a rabbit secondary magnetic resonance imaging to a presumptive ischemic infarct. Strokes should be included in the differential diagnosis of central vestibu- lar syndrome in rabbits. a  Hospital Clínic Servei de Neurologia, Fundacio © 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license Veterinari, Campus Universitat Autonoma de (http://creativecommons.org/licenses/by-nc-nd/4.0/) Barcelona, Bellaterra, Spain b Departament de Medicina i Cirurgia Animal, ria, Edifici V, Universitat Facultat de Veterina noma de Barcelona, Bellaterra, Spain Auto c stic per la Imatge, Fundacio Servei de Diagno  Hospital Clínic Veterinari, Campus Universitat Auto noma de Barcelona, Bellaterra, Spain d tics, Fundacio Servei d’Exo  Hospital Clínic Veterinari, Campus Universitat Autonoma de Barcelona, Bellaterra, Spain Introduction range: 38°-40°C). Neurological examination showed an alert mental status, a left head tilt, reluctance to walk with left vestibular ataxia, Central vestibular disease is common in pet rabbits, and head tilt and a tendency to fall to the left side. Postural reactions were severely is the most common clinical sign.1 Although different etiologies have delayed in the right thoracic and pelvic limbs. Cranial nerve evalua- been reported, meningoencephalitis caused by Encephalitozoon cuni- tion was normal except for a ventral positional strabismus of the left culi (E cuniculi) infection appears to be the most frequent2 Other eye and a bilateral rotary nystagmus with the fast phase to the left. causes are rarely recognized. Several articles describe the effects of Spinal reflexes were considered normal and there were no signs of artificially induced vascular occlusion of rabbit cerebral vessels3-5 but spinal hyperesthesia. The remainder of the physical and neurological reports of naturally occurring cerebrovascular accidents are lacking examinations were unremarkable. The neurological examination was in small mammal medicine. To the authors knowledge, this is the first considered consistent with a right central (paradoxical) vestibular report of a presumptive cerebellar infarct in a rabbit diagnosed by syndrome. Initial differential diagnoses included neoplastic, inflam- magnetic resonance imaging (MRI). matory/infectious, or vascular diseases. Blood tests (complete blood cell count, serum biochemistry) were within normal values. Thoracic and abdominal radiographs and Case Presentation abdominal ultrasonography did not show any abnormalities. A brain MRI was performed using a 0.4 T permanent magnet unit A 6-year-old, female spayed, domestic rabbit (Oryctolagus cunicu- (Hitachi Aperto Lucent Hitachi Medical Systems, Madrid, Spain). A stan- lus) was presented for an acute onset of rolling to the left. The rabbit’s dardized protocol was used (T2W: TR = 3140 4262 ms, TE = 100 ms, diet consisted mainly of unlimited amounts of hay and daily fruits slice thickness = 3 mm; FLAIR: TR = 8000 ms, TE = 90 ms, slice thick- and vegetables. Pellets were restricted. She was housed in a big cage ness = 3 mm; T2*W: TR = 500, TE = 40 ms, slice thickness = 3 mm; T1W: with solid floor and side wires. Physical examination revealed a good TR = 582 ms, TE = 13 ms, slice thickness = 3 mm). Gadolinium (Dotarem body condition of 3/5, a heart rate of 240 beats per minute (reference 0.5 mmol/mL, Dotarem-Guerbet Laboratories: Madrid, Spain) was used range:154-300), a respiratory rate of 200 breaths per minute (refer- as contrast agent at a dose of 0.2 mL/kg IV. DWI was not performed and ence range: 30-60), and a body temperature of 37.8°C (reference cerebrospinal fluid was not collected in order to shorten the anesthetic time because the patient became hemodynamically unstable. *Corresponding author. Sonia An ~ or, DVM, PhD, Dip ACVIM (Neurology), Dip ECVN, ria, Edifici V, Universi- The MRI study showed an intra-axial lesion with well-defined Departament de Medicina i Cirurgia Animal, Facultat de Veterina  noma de Barcelona, Bellaterra 08193, Spain tat Auto margins and a triangle-shaped appearance on transverse images, ~ or). E-mail address: sonia.anor@uab.cat (S. An located in the rostromedial portion of the right cerebellar hemisphere Abbreviations: E. cuniculi, Encephalitozoon cuniculi; MRI, Magnetic resonance imaging; and the right side of the vermis. Compared to gray matter, the lesion T2W, T2 weighted; T1W, T1 weighted; FLAIR, Fluid attenuated inversion recovery; TR, was hyperintense on T2W, FLAIR and T2* images. On T1W images, Repetition time; TE, Echo time; DWI, Diffusion weighted imaging; ADC, Apparent diffu- sion coefficient; CSF, Cerebrospinal fluid; CNS, Central nervous system the lesion was hypointense and showed no contrast enhancement. A http://dx.doi.org/10.1016/j.tcam.2021.100509 1938-9736/© 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) 2 R. García et al. / Topics in Companion An Med 43 (2021) 100509 mild mass effect that caused a midline shift toward the left was also central nervous system infections causing signs of peripheral observed. These MRI findings were consistent with an ischemic disfunction.1,7 infarct in the territory of the right rostral cerebellar artery (Fig 1). Paradoxycal vestibular syndrome has never been reported in this Other less likely differential diagnoses included inflammatory/infec- species regardless of the underlying cause and it is not frequent tious encephalitis or infiltrative neoplasia such as lymphoma. either in small animals. However, in the cases described, inflamma- Thromboelastography was performed in order to assess hemosta- tory disease or neoplasia are the most frequent final diagnoses.8 sis and it was unremarkable. Echocardiography was encouraged but The most common cause of central vestibular disease in rabbits is rejected by the owner. granulomatous encephalitis caused by the microsporidian E cuniculi A serologic test for E cuniculi was also performed and it was posi- and it is frequently transmitted through ingestion of spores. The way tive (IgM 1:480; IgG 1:1280). the patient of this report was infected is unknown, although the The patient was hospitalized for 3 days and fluid-therapy was started microsporidian could have been latent since adoption and reactivate using crystalloid fluids (Ringer Lactate Braun 500 mL, Braun, Kronberg, later on. Even if there is a high percentage of rabbits seropositive to Germany)) at a maintenance rate of 4 mL/kg/h IV, and she was placed in the parasite (50%-70%),7 it is frequent that the infection is chronic an oxygen cage in order to maintain brain perfusion and to avoid cerebral and asymptomatic,1 so the fact that both serological titers were ele- hypoxia. Assisted feeding was initiated with a commercial powdered vated did not necessarily indicate that encephalitozoonosis was the preparation (Oxbow Critical Care, Oxbow Animal Health: NE). The patient cause of the clinical signs. In addition, there is no correlation between showed significant improvement during hospitalization and was dis- the severity of the E cuniculi-induced histopathological lesions in the charged 3 days later with fenbendazole at 20 mg/kg/PO every 24 hours brain and neurological signs.9 for 28 days (Panacur 100 mg/mL, MSD Animal Health, Salamanca, Other reported causes of central vestibular syndrome in rabbits Espan~ a). Although the authors consider E cuniculi unlikely to be the cause include intracranial neoplasms such as lymphoma or other inflamma- of the clinical signs, treatment was instituted because it is highly recom- tory encephalopathies, but vascular lesions have not been identified mended when serological titers are elevated and indicate active infection. as primary causes of vestibular syndrome in rabbits and the few men- A gradual improvement in neurological signs was observed on weekly tions on vascular lesions causing neurological signs are secondary to rechecks performed during the first 2 months. Five months later, the rab- hypoxia.2 This lack of evidence of ischemic infarcts in rabbits can be bit had no clinical signs of vestibular disease. due to the fact that brain MRI is not routinely performed in patients with vestibular disease and the diagnosis usually relies on more basic testing like radiographs of the tympanic bullae and serology for E Discussion cuniculi infection. It is widely known that MRI is more expensive and requires long times of anesthesia, sometimes leading caregivers to Vestibular syndrome is the most common neurological abnormality choose a more conservative diagnostic approach that might be incon- in rabbits, and it has been traditionally classified as peripheral or cen- clusive. It is currently unknown whether granulomatous encephalitis tral. To differentiate peripheral from central vestibular syndrome can caused by E cuniculi can predispose to ischemic infarcts in rabbits. be challenging, but sensitivity of the neurological localization rises up Ischemic infarcts are more frequently included in the differential diag- to 90% in small animals when it is performed accurately.6 Performance nosis of dogs with acute, nonprogressive central vestibular signs, paradox- of an accurate neurological examination in pet rabbits is specially chal- ical or not.10 Predisposing factors in canines include endocrinopathies lenging given their prey nature and their tendency to remain still (Cushing’s syndrome, diabetes mellitus, and hypothyroidism) or chronic when they feel stressed or uneasy and even more when rabbits are renal failure. However, an underlying cause cannot be found in up to 50% rolling.1 In addition, differentiation of central and peripheral vestibular of dogs with brain infarction.11 The tests performed in the rabbit pre- syndrome can also be difficult due to the high frequency of E cuniculi sented here did not show any results compatible with endocrinopathies Fig 1. MRI findings. The following MR images are at the cerebellomedullary junction. Note the extensive, well-demarcated lesion in the right cerebellar hemisphere that is hyperin- tense on T2W (A), FLAIR (B), and T2* (D) images, and hypointense on T1W (C), without contrast enhancement (E). R. García et al. / Topics in Companion An Med 43 (2021) 100509 3 and thromboelastography was normal, so unfortunately no factors that rabbits. MRI is essential for diagnosis and should be included in the diag- could lead to a prothrombotic status could be identified. nostic protocol of central neurological disease in rabbits. The rabbit’s cerebellar vascular supply is carried by 2 sets of arteries. The caudal cerebellar artery (right and left), which origi- Authors’ Contributions nates from the basilar artery, and the rostral cerebellar artery (right and left) that has its origin in the caudolateral aspect of the RG was an assistant clinician and wrote the article. VS was the pri- circle of Willis. In a small percentage of animals, the right internal mary clinician of the case. RN performed the magnetic resonance, carotid artery sends a vessel at the level of the cerebellar informed the images and reviewed the article. SA supervised the case peduncles that anastomoses with the terminal portion of the basi- and reviewed the article. JM supervised the case and reviewed the lar artery, creating the right rostral cerebellar artery. The rostral article. CF reviewed the article. cerebellar artery is usually double on the right side and single on the left. In cases in which it is double, it vascularizes almost the References entire cerebellum. The caudal cerebellar artery is often single and can be found at the trapezoid body generating a lateral branch of 1. Ku€ nzel F, Gruber A, Tichy A, Edelhofer R, Nell B, Hassan J, Leschnik M, Thalhammer JG, Joachim A. Clinical symptoms and diagnosis of encephalitozoonosis in pet rab- the basilar artery. It can also be double or triple in some cases.12 bits. Vet Parasitol 151:115–124, 2008 Therefore, and despite some differences, the cerebellar vascular 2. Gruber A, Pakozdy A, Weissenbo € ck H, Csokai J, Ku € nzel F. A retrospective study of supply in rabbits is similar to that in canines. In dogs, most ische- neurological disease in 118 Rabbits. J Comp Pathol 140:31–37, 2009 3. Cheng L, Guo P, wei Liao Y, liang Zhang H, ting Li H, Yuan X. 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Csokai J, Gruber A, Ku € nzel F, Tichy A, Joachim A. Encephalitozoonosis in pet rabbits not performed for the reasons aforementioned, the MRI study was (Oryctolagus cuniculus): pathohistological findings in animals with latent infection consistent with an infarct, showing features similar in shape, inten- versus clinical manifestation. Parasitol Res 104:629–635, 2009 sity, and localization to those in dogs. 10. Thomsen B, Garosi L, Skerritt G, et al. Neurological signs in 23 dogs with suspected rostral cerebellar ischaemic stroke. Acta Vet Scand 58:1–9, 2016 Prognosis in canines with strokes is considered fair to good with a 11. Garosi L, McConnell JF, Platt SR, et al. Results of diagnostic investigations and long- survival rate of approximately 60%.11 The clinical progression of the term outcome of 33 dogs with brain infarction (2000-2004). J Vet Intern Med rabbit reported here, despite treatment for encephalitozoon, resem- 19:725–731, 2005 12. de Souza F, Campos R. 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