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Computed tomographic features of clinical and subclinical middle ear disease in domestic rabbits (Oryctolagus cuniculus): 88 cases (2007–2014) Ricardo de Matos, LMV; Jennifer Ruby, DVM; Ruth A. Van Hatten, DVM; Margret Thompson, DVM Objective—To describe and compare CT abnormalities of the middle ear in rabbits (Oryctolagus cuniculus) that had clinical or subclinical middle ear disease and to determine the prevalence of otitis media and evaluate the role of predisposing factors for otitis media in that species. Design—Retrospective case series. Animals—88 domestic rabbits. Procedures—Medical records for rabbits that underwent CT of the head in June 2007 through February 2014 were searched and classified on the basis of reason for head CT (ie, ear-related disease vs non–ear-related disease). The ears, upper respiratory tract, teeth, and other important structures of each rabbit’s head were evaluated. Follow-up information was obtained for rabbits with CT abnormalities of the middle ear without clinical signs (ie, subclinical disease). Results—12 of 21 (57%) rabbits with clinical signs of ear disease and 18 of 67 (27%) rabbits without clinical signs of ear disease had CT abnormalities of the middle ear. In CT images, all affected ears had soft tissue–attenuating material within the tympanic bulla. Tympanic bulla lysis was associated with clinical middle ear disease. Most (12/18) rabbits with subclinical middle ear disease remained subclinical after CT examination. Middle ear CT-detected changes and lop-ear conformation or otitis externa were strongly correlated; middle ear disease and upper respiratory tract disease were not correlated. Conclusions and Clinical Relevance—Data suggested that subclinical otitis media frequently affects rabbits, and those with bulla lysis should be closely monitored. Lop-eared rabbits and rabbits with otitis externa had a higher risk of developing otitis media. (J Am Vet Med Assoc 2015;246:336–343)
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titis media, or inflammatory disease of the middle ear, in rabbits is commonly reported.1–3 Otitis media can be difficult to diagnose in live rabbits because those with otitis media are often subclinically affected unless the disease is associated with otitis externa or interna.1,3–7 Postmortem studies1,4 investigating subclinical otitis media in rabbits have indicated prevalences ranging from 11.5%8 to 32%. With otitis interna, rabbits develop signs of vestibular disease.4,9–12 Reports vary with respect to the prevalence of otitis media in rabbits with vestibular disease: 5.5% in a postmortem study13 of rabbits with neurologic disease, 24% in an Encephalitozoon cuniculi seroprevalence study,14 and 63% in a postmortem study12 of rabbits with vestibular disease. Most of these studies determined prevalence of subclinical and clinical middle ear disease in rabbits at necropsy, not on an antemortem basis, and in meat rabbits or research rabbits, not in domestic rabbits. Examination of the external ear canal and tympanic membrane has been proposed for diagnosis of subclinical otitis media. However, neither an apparently normal tympanic membrane nor an apparently normal external ear canal excludes the presence of otitis media.1,4,15 In adFrom the Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853. Address correspondence to Dr. de Matos ([email protected]). 336
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dition, examination of the tympanic membrane can be challenging, especially in rabbits with otitis externa and in lop-eared rabbits.6,16 Early diagnosis of otitis media is extremely important because infection can spread to the inner ear (causing vestibular disease due to labyrinthitis) or through the internal acoustic meatus and along the vestibulocochlear nerve to the brain (resulting in severe neurologic signs due to encephalomyelitis).4,9–13 Rabbits with otitis interna develop clinical signs of peripheral vestibular disease, including head tilt, nystagmus, ataxia, or rolling.2 Facial nerve paralysis and Horner’s syndrome can also develop with otitis media or interna in rabbits.2 Otogenic intracranial infection in humans17 and in dogs and cats18 is reported to be rare. However, it is relatively common in rabbits, affecting up to 50% of rabbits with otitis media.12,13 In those cases, clinical signs of central vestibular disease may be preceded by signs of peripheral vestibular disease, making distinction between central and peripheral vestibular diseases difficult.10,18 The main differential diagnosis for rabbits with central vestibular signs is E cuniculi infection.10–13 Even though serologic tests are available for anti–Pasteurella multocida and anti– E cuniculi antibodies, positive results of assays for serum antibodies reflect exposure and do not correlate with active disease caused by either organism.10,11,13 Owing to the often subclinical signs of otitis media, the difficulty in differentiating otitis media or interna JAVMA, Vol 246, No. 3, February 1, 2015
Materials and Methods Case selection—The medical records for rabbits that were evaluated at the Cornell University Hospital for Animals from June 2007 to February 2014 were searched for those that underwent CT of the head. Information collected from each medical record included age, weight, sex, ear conformation, past medical history, reason for visit, and physical examination findings. Rabbits that underwent head CT were assigned to 1 of 2 groups according to the reason for their visit. Group 1 included rabbits evaluated because of clinical signs of otitis externa (head JAVMA, Vol 246, No. 3, February 1, 2015
shaking, pinnal pruritus, malodorous ears, or, for rabbits with upright ears, holding the affected ears down) or middle ear disease (signs of vestibular disease or facial nerve paralysis). Group 2 included rabbits evaluated for conditions not related to ear disease (dental disease, upper respiratory tract disease, and other conditions of the head region, such as ocular or periocular disease or soft tissue or bone masses). CT examinations—All head CT examinations were performed after each rabbit was sedated with ketamine (10 mg/kg [4.5 mg/lb]) and diazepam (0.5 mg/kg [0.23 mg/lb], IV) or anesthetized with isoflurane with oxygen delivered via face mask. Computed tomographic scans were obtained with a single-slice axial CT unita (for cases examined between August 2008 and July 2009) or a 16-slice helical CT unitb (for cases examined between August 2009 and March 2014). Images were acquired in 0.5- to 1-mm contiguous transverse slices (120 kVp; mAs set automatically) with rabbits positioned in ventral recumbency. Most scans were performed with a soft tissue and bone algorithm (72/88 rabbits), with a few performed with a bone algorithm only (15/88 rabbits) or a soft tissue algorithm only (1/88 rabbits). Image evaluation—External, middle, and inner portions of the ear were evaluated for each rabbit by a board-certified radiologist (MT) and a radiology resident (RAVH). Image evaluation was performed in chronological order of CT examinations. Reviewers were blinded to the rabbit’s group assignment, the reason for head CT, and the other reviewer’s interpretation of ear CT-detected changes. Once the image review process was completed, inter-reviewer discrepancies were addressed with collaborative image evaluation during which both reviewers agreed on a single diagnosis. Images were interpreted on a commercial picture archiving and communication systemc with multiple planes and windows available. The external ear was evaluated for increased attenuation within the canal, thickness of the wall of the external ear canal, mineralization of the auricular cartilages, and presence of a mass or masses within or associated with the external ear canal. The middle ear was evaluated for the presence of attenuating material within the tympanic cavity or increased thickness, irregularity, expansion, or lysis of the tympanic cavity wall. The inner ear was evaluated for sclerosis or lysis of the petrous temporal bone or loss of cochlear semicircular canal definition. Lesions of the external, middle, and inner ear were categorized as absent or present on CT images. In addition, abnormalities in the upper respiratory tract and teeth and other remarkable findings within the head region were recorded. Follow-up—Information regarding the progression of subclinical middle ear disease in affected rabbits was obtained by follow-up visits or telephone or email contact with the owners or referring veterinarians. When available, findings of a follow-up CT ear examination were also recorded, characterized, and compared with the initial CT findings. Data analysis—Descriptive statistics were used for data analysis and calculated in spreadsheet softwared (numeric data) and an online data analysis programe Scientific Reports
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from central vestibular disease, and the relatively high prevalence of otogenic intracranial infection, diagnostic imaging is important for evaluation of the middle ear and early identification of middle ear disease in rabbits. Computed tomography allows cross-sectional evaluation of the entire head, including teeth and upper respiratory tract, without superimposition of structures.19–24 Computed tomography is reported to be more sensitive than, and as specific as, radiography for diagnosing and characterizing the severity of middle ear disease in dogs.25 Computed tomographic findings of otitis media in dogs and cats include thickening, irregularity, proliferation, or lysis of the tympanic bulla wall. In addition, a fluid or soft tissue density may be evident within the lumen of the bulla.19,20,26 The use of CT for diagnosis of otitis media in rabbits has been described in the veterinary medical literature.6,7,11,24,27,28 However, the information is descriptive and limited to CT-detected changes in clinical cases of otitis media. In rabbits with otitis media, the primary infection is believed to be a result of bacteria within the nasopharynx that reach the middle ear via the auditory tube.1,4,10 This pathogenesis is supported by the fact that most infections are caused by P multocida, a respiratory tract pathogen.1,3,4,8,9,11,12,29 In addition, high prevalences of middle ear disease in rabbits with concurrent upper respiratory tract infections have been reported (78%4 and 85%8). Otitis media also develops secondary to bacterial or parasitic otitis externa.1,15,30,31 Otitis externa develops more commonly in lop-eared rabbits, possibly because of abnormal conformation of the external ear canal.15 The purpose of the study reported here was to describe and compare CT abnormalities in the middle ear of domestic rabbits (Oryctolagus cuniculus) that had clinical middle ear disease with those in rabbits without signs of disease (subclinical disease) and to determine the prevalence of otitis media in that species. Because there are multiple possible causes of otitis media in rabbits that are not fully understood, another aim was to evaluate the frequency of proposed predisposing factors of otitis media (upper respiratory tract disease, otitis externa, and lop-ear conformation) in rabbits with subclinical or clinical otitis media and in rabbits with or without otitis media. We hypothesized that CT signs of otitis media are a common finding in rabbits that undergo head CT for reasons other than ear disease, that CT middle ear abnormalities would differ between rabbits with clinical and subclinical otitis media, and that predisposing factors to otitis media would be detected more commonly in rabbits with clinical and subclinical otitis media than in rabbits without otitis media.
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(categorical data). Numeric data (age and weight) were described as mean ± SD. Categorical data (presence or absence of CT-detected changes of the external, middle, or inner ear; unilateral or bilateral disease; type of lesion present in the middle ear; ear conformation; and upper respiratory tract disease) were described as the frequency of occurrence of each category by group. Depending on sample size, Fisher exact tests or χ2 tests were used to determine the association between the type of CT middle ear lesion and reason for visit (groups 1 and 2) and, within group 2, between rabbits with permanent and temporary subclinical middle ear disease. These same tests were used to determine the association between middle ear disease (clinical vs subclinical and presence vs absence) and the proposed middle ear predisposing factors (lop-ear conformation, otitis externa, and upper respiratory tract disease). Values of P < 0.05 were considered significant. Results Case selection—Eighty-eight of 784 rabbits evaluated from June 2007 to February 2014 met the inclusion criteria. Twenty-one (24%) rabbits were evaluated because of ear disease or signs suggestive of ear disease (group 1). Clinical signs in group 1 included clinical otitis externa (n = 6), facial nerve paralysis (3), and signs of vestibular disease (20). The group included 9 (43%) males and 12 (57%) females. These rabbits had a mean ± SD age of 4.4 ± 2.6 years (range, 0.1 to 8 years) and mean weight of 1.9 ± 0.92 kg (4.2 ± 2.0 lb; range, 0.6 to 4.9 kg [1.3 to 10.8 lb]). Sixty-seven (76%) rabbits included in the study were evaluated because of other conditions not related to or suggestive of ear disease (group 2). Clinical problems in group 2 included dental disease (n = 33), upper respiratory tract disease (18), and other conditions involving the skull or head (16). Group 2 included 47 (70%) males and 20 (30%) females. Rabbits in group 2 had a mean age of 4.9 ± 2.51 years (range, 0.2 to 11.6 years) and mean weight of 2.26 ± 0.9 kg (5.0 ± 2.0 lb; range, 0.7 to 5.3 kg [1.5 to 11.7 lb]). Prevalence of CT-detected middle ear changes— Twelve of the 21 (57%) rabbits in group 1 had CT abnormalities of the middle ear (Table 1). Among the 20
rabbits with signs of vestibular disease in group 1, 11 (55%) had CT-detected changes consistent with middle ear disease; the other 9 (45%) had no CT-detected changes in the external, middle, or inner ears, and presumptive central vestibular disease was diagnosed. Eighteen of the 67 (27%) rabbits in group 2 had CT abnormalities of the middle ear. Characterization of CT abnormalities of the middle ear—For group 1 rabbits with CT-detected changes of the middle ear, 6 had unilateral changes and 6 had bilateral changes (overall, 18 affected ears; Table 1). All those affected ears had soft tissue attenuating material (ie, increased attenuation) within the tympanic bulla; of the 18 ears, 10 had lysis of the bulla (prevalence, 55%) and 3 had thick tympanic bulla (Figure 1). The 3 rabbits in group 1 with facial nerve paralysis had CTdetected changes of the middle ear. One rabbit had middle ear changes ipsilateral to facial nerve paralysis and no vestibular signs. The other 2 rabbits had bilateral middle ear changes as well as head tilt and facial nerve paralysis ipsilateral to inner ear CT-detected changes. The type and severity of middle ear CT-detected changes in rabbits with facial nerve paralysis were similar to the findings for other rabbits in group 1 that had signs of vestibular disease without facial nerve paralysis. Five of the group 1 rabbits with signs of vestibular disease and CT-detected changes of the middle ear had unilateral disease and ipsilateral vestibular signs. The remaining 6 rabbits with signs of vestibular disease and CT-detected changes of the middle ear had bilateral middle ear disease. Vestibular signs were ipsilateral to the ear with more severe middle ear CT lesions (2 cases) or to the ear with inner ear changes detected with CT (2 cases). The 2 remaining rabbits with vestibular signs had bilateral middle and inner ear disease. Despite similar CT abnormalities and severity of disease for both middle and inner ears, those rabbits had unilateral vestibular signs. Among the 18 group 2 rabbits with CT evidence of middle ear disease (ie, relevant CT abnormalities) but no clinical signs, 10 had unilateral subclinical disease and 8 had bilateral subclinical disease (overall, 26 affected ears; Table 1). All affected middle ears of rab-
Table 1—Prevalence of middle, external, and inner ear CT-detected changes in 88 domestic rabbits (Oryctolagus cuniculus) that had clinical middle ear disease and those without signs of middle ear disease (subclinical disease). Rabbits with subclinical disease Rabbits with clinical disease
Variable
All
Rabbits with upper respiratory tract disease
33/67
Rabbits with other problems
Total No. of rabbits
21/88
67/88
No. of rabbits with CT-detected middle ear changes (%) No. of rabbits unilaterally affected (%) No. of rabbits bilaterally affected (%)
12/21 (57) 6/12 (50) 6/12 (50)
18/67 (27) 10/18 (56) 8/18 (44)
7/18 (39) 0/7 (0) 7/7 (100)
8/33 (24) 7/8 (88) 1/8 (13)
3/16 (19) 3/3 (100) 0/3 (0)
No. of rabbits with CT-detected external ear changes (%) No. of rabbits unilaterally affected (%) No. of rabbits bilaterally affected (%)
10/21 (48) 2/10 (20) 8/10 (80)
32/67 (48) 3/32 (9) 29/32 (91)
11/18 (61) 0/11 (0) 11/11 (100)
15/33 (45) 1/15 (7) 14/15 (93)
6/16 (38) 2/6 (33) 4/6 (67)
4/21(19) 2/4 (50) 2/4 (50)
2/67 (3) 2/2 (100) 0/2 (0)
1/18 (6) 1/1 (100) 0/1 (0)
1/33 (3) 1/1 (100) 0/1 (0)
0/16 (0) NA NA
No. of rabbits with CT-detected inner ear changes (%) No. of rabbits unilaterally affected (%) No. of rabbits bilaterally affected (%)
18/67
Rabbits with dental disease
16/67
NA = Not applicable. 338
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the head was repeated for evaluation of chronic upper respiratory tract disease, and no progression of middle ear lesions was detected (Figure 3). On comparison of middle ear CT lesions between group 2 rabbits that remained subclinical and rabbits that eventually developed clinical signs of middle ear disease, the prevalence of attenuation and thickening of the tympanic bulla was similar. However, rabbits that eventually developed clinical signs had a higher prevalence of bulla lysis, compared with rabbits that remained subclinically affected (3/5 vs 1/10). Nevertheless, the difference in prevalence of lytic changes of the bulla between these 2 subgroups was not significant (P = 0.262). The presence of CT-detected changes of the external and inner portion of the ear was also recorded for rabbits in both groups (Table 1). Four rabbits in group 1 had CTdetected changes in all 3 portions of the ear (external, middle, and inner ear). Both group 2 rabbits with inner ear CT-detected changes had no vestibular signs before or at the time of CT examination. One rabFigure 1—Transverse (A and C) and dorsal (B) CT images at the level of the tympanic bit remained subclinical for 4 months after bullae of a 7-year-old spayed female lop-eared rabbit (Oryctolagus cuniculus) that had sudden-onset right head tilt and mild right facial nerve paralysis. The images are dis- CT (but was euthanized by IV injection of played in a bone (A and B) or soft tissue (C) algorithm and were obtained in 1-mm pentobarbital sodium solution because of contiguous slices. Both external ear canals are expanded with a soft tissue–attenuat- progression of dental disease). The other ing material. The left external ear canal is replaced by a large soft tissue–attenuating rabbit developed vestibular signs ipsilateral mass that expands from the left middle ear, causing local disruption and lysis of the left tympanic bulla and left inner ear. The right tympanic bulla is filled with soft tissue– to the affected inner ear 3 days after the CT attenuating material, but the normal structure of the bulla is maintained, and lysis of examination. These signs resolved within the petrous temporal bone is not detected. R = Right. 2 days, during which time antimicrobial treatment for an upper respiratory tract infection was administered. Two years later, the rabbit conbits in group 2 had increased attenuation within the tinued to have no recurrence of vestibular signs. tympanic cavity. The prevalence of bulla lysis was 19% (5/26), and that of increased bulla thickness was 19% Predisposing factors for middle ear disease—Of (5/26). Comparing the prevalence of CT-detected midthe 21 rabbits in group 1, 9 (43%) were lop-eared rabdle ear changes between the 2 groups, the prevalence bits. Of the 12 rabbits in group 1 with CT-detected of bulla lysis in rabbits with clinical middle ear disease middle ear changes, 9 had lop ears and 3 had upright (group 1) was significantly (P < 0.001) higher. ears. All rabbits with presumptive central vestibular One rabbit with subclinical middle ear CT disease disease had upright ears. For group 2, the distribution was euthanized by IV injection of pentobarbital sodium of lop-eared rabbits (28/67 [42%]) was similar to that solution during the CT examination because of advanced in group 1. Of the 18 rabbits with CT-detected changes dental disease. Follow-up information was available for of the middle ear in group 2, 12 had lop ears and 6 had all other rabbits with subclinical middle ear disease, with upright ears. Combining rabbits with clinical or suba median monitoring time after CT examination of 23 clinical middle ear disease (30 rabbits), 21 (70%) had months (range, 2 months to 5 years). Five of 17 group 2 lop ears and 9 (30%) had upright ears. For the 58 rabrabbits with CT abnormalities of the middle ear eventubits with no CT-detected middle ear changes, 16 (28%) ally developed temporary (n = 2) or persistent (3) signs had lop ears and 42 (72%) had upright ears. Although of peripheral vestibular disease after CT (median interthere was no association between ear position and clinival after CT examination, 10 months [range, 3 days to 2 cal or subclinical ear disease, there was a significant (P years]). A CT scan of the head was repeated in 2 of the < 0.001) association between lop ears and presence of rabbits that developed persistent vestibular signs, and CT-detected changes of the middle ear. The study data images confirmed the progression of middle ear disease indicated a significant association between upright ears in comparison with the initial CT findings (Figure 2). and presumptive central vestibular disease. The remaining 12 rabbits with CT abnormalities of the Of the 12 rabbits in group 1 with CT-detected changmiddle ear but no signs of middle ear disease did not es of the middle ear, 10 also had CT abnormalities of the develop signs suggestive of ear disease after CT examinaexternal ear; 2 had only middle ear changes. No rabbits in tion (median interval after CT examination, 9 months this group had CT-detected changes limited to the exter[range, 2 months to 5 years]). For 2 of the rabbits that nal ear. For group 2, 15 of the 18 rabbits with CT-detected remained subclinically affected, CT examination of
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Figure 2—Transverse CT images (obtained over a period of 13 months) at the level of the tympanic bullae of a 2-year-old sexually intact male Miniature Rex rabbit with chronic upper respiratory tract infection. A—The image is displayed in a bone algorithm; images were obtained in 1-mm contiguous slices at the initial evaluation. Bilateral otitis media is evident with both bullae occupied by a soft tissue– attenuating material and lysis present at the lateral aspect of the right tympanic bulla. The inner ears are unaffected. B—Image obtained 10 months later when the rabbit was evaluated because of a right head tilt and worsening upper respiratory infection. The bilateral otitis media has advanced to include expansile lytic lesions along both tympanic bullae, with the right being more severely affected than the left. The inner ears remain unaffected. C—Image obtained 13 months after the first CT examination when the rabbit developed neurologic clinical signs after discontinuing medications. The bilateral otitis media remains severe as before. There is a new development of lysis of the left inner ear; however, the right inner ear remains unaffected. R = Right.
upper respiratory tract disease and had CT abnormalities of the upper respiratory tract. For group 2 rabbits, prevalences of middle ear disease by reason for head CT were summarized (Table 1). Rabbits with signs of upper respiratory tract disease had a higher prevalence of CT-detected changes of the middle ear, with all rabbits having bilateral disease. However, the difference in prevalence of CT changes of the middle ear with regard to the different reasons for head CT in group 2 rabbits was not significant. Combining rabbits with subclinical Figure 3—Transverse CT images at the level of the tympanic bullae of a 2-year-old and clinical middle ear disease (30 cases), castrated male Miniature Holland Lop rabbit with chronic upper respiratory tract disease and mild left facial nerve paralysis. The images are displayed in a bone algorithm 10 (33%) had CT-detected changes conand were obtained in 1-mm contiguous slices. A—Both tympanic bullae are occupied sistent with upper respiratory tract disby a soft tissue–attenuating material, and both inner ears appear intact. Additional ease or a history of upper respiratory tract images in the CT scan revealed severe, destructive rhinopathy on the right (image not shown). B—Image obtained from same rabbit in panel A 2 years later to evaluate the disease, and 20 (67%) had neither CTchronic upper respiratory tract disease. The bilateral otitis externa and media are un- detected changes within the upper respichanged, and the destructive rhinopathy is progressive (image not shown). R = Right. ratory tract nor a history of upper respiratory tract disease. Among the 58 rabbits with no middle ear changes identified by CT, 20 (34%) middle ear lesions had CT-detected abnormalities of the had CT-detected changes consistent with upper respiraexternal ear, with 3 having only middle ear changes. In tory tract disease or a history of upper respiratory tract contrast, 17 of 32 (53%) rabbits with CT-detected external disease, and 38 (66%) had neither CT-detected changes ear lesions had no CT-detected lesions in the middle ears. within the upper respiratory tract nor a history of upper None of these rabbits developed signs of otitis externa, respiratory tract disease. There was no significant (P = media, or interna following CT examination. Combining 0.88) association between upper respiratory tract disease rabbits with subclinical and clinical middle ear disease (30 and presence of middle ear CT abnormalities. cases), 25 (83%) rabbits had CT-detected changes in the In group 2, 12 rabbits had CT-detected changes of the external ear, and 5 (17%) had apparently normal extermiddle ear, and their disease remained subclinical, and 5 nal ears. For rabbits with no middle ear CT abnormalirabbits with subclinical disease eventually developed vesties (n = 58), 17 (29%) rabbits had CT-detected changes tibular signs. Analysis of those data revealed no significant in the external ear, and 41 (71%) had apparently normal association between progression of disease and ear position, external ears. Although the prevalence of otitis externa in presence of external ear disease, or reason for head CT. groups 1 and 2 was the same, there was a significant (P < 0.001) association between otitis externa and presence of CT-detected changes of the middle ear. Discussion Only 3 of 12 rabbits in group 1 with CT-detected The overall prevalence of clinical middle ear dischanges of the middle ear had a history of upper respiratory ease in rabbits in this retrospective study was 57%. For tract disease (2 rabbits) or had CT abnormalities of the uprabbits with vestibular signs, the prevalence was 55%. per respiratory tract (1 rabbit). For group 2, 7 of 18 rabbits Different prevalences (5.5%,13 24%,14 and 63%12) of with CT-detected changes of the middle ear had a history of 340
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inner ear disease.38 It is possible that changes in the inner ear of these rabbits were subtle or limited to the soft tissue portion, which would be more readily detected by CT with contrast agent administration or MRI.20,28 In the present study, there was no association between the characteristics of the CT-detected middle ear changes and the occurrence of facial nerve paralysis. Facial nerve paralysis is not specific to ear disease and can develop in rabbits with abscesses or other masses in the nerve pathway.39 For rabbits with subclinical middle ear disease (group 2) in the present study, unilateral middle ear changes were more prevalent than bilateral middle ear changes (56% vs 44%). Previous reports describe a higher prevalence of bilateral subclinical otitis media in meat (70%1) and research (81%3) rabbits. As for other findings, discrepancies in these prevalences may be due to differences in rabbit populations, medical history, or method of diagnosis of otitis media. Two rabbits in group 2 had unilateral CT-detected changes of the inner ear and no vestibular signs before CT examination. In contrast, all rabbits in group 1 with CT-detected changes of the inner ear had persistent vestibular signs. Although it is possible that changes in the inner ear of the group 2 rabbits were limited to the bone structures of the inner ear, CT with contrast agent administration or MRI would have been helpful to more accurately evaluate the soft tissue portion of the inner ear and compare clinical and subclinical inner ear disease.28 The clinical relevance of CT abnormalities of the middle ear in rabbits with subclinical disease remains unknown. Seventy-one percent of rabbits with CTdetected changes of the middle ear remained subclinically affected after the CT examination in the present study. The reason for head CT, ear position, or presence of CT-detected external ear lesions was not associated with progression of subclinical ear disease. Rabbits with subclinical middle ear disease that eventually developed vestibular signs had a higher prevalence of bulla lysis, compared with rabbits that remained subclinically affected. Although the association was not significant (perhaps because of the small sample size), the authors recommend close monitoring (including CT examination) of rabbits with subclinical middle ear disease that have lysis of the tympanic bulla revealed by CT. Three proposed predisposing factors for the development of middle ear disease in rabbits were investigated in the present study: ear position, otitis externa, and upper respiratory tract disease. No significant association was found between ear position and the development of clinical or subclinical middle ear disease. However, the study results supported an association between CT-detected middle ear changes and lop-ear conformation and between central vestibular disease and upright-ear conformation. Similarly, a strong association was evident between external ear and middle ear changes identified by CT. It is unknown whether CT-detected changes within the external ear in rabbits with CT-detected lesions in the middle ear were a cause or consequence of middle ear disease in the rabbits in group 1. It is important to note that no rabbits in group 1 had CT-detected changes of the external ear alone, and 17 of 32 (53%) rabbits with external ear disease, as Scientific Reports
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clinical middle ear disease in rabbits have been previously reported. Among the various studies, these discrepancies are likely attributable to differences in rabbit populations, inclusion criteria, or method of diagnosis of otitis media. For the study14 that found a prevalence of 24%, diagnosis was based on otoscopic examination findings and radiographic abnormalities. The higher prevalence of middle ear disease reported in the present retrospective study could be due to the increased sensitivity and accuracy of CT for identifying changes of the middle ear, compared with routine radiography, as previously reported.25,32,33 One limitation of the present study and the one by Jeklova et al14 was that the imaging abnormalities of the middle ear were not confirmed during surgery, by histologic evaluation, or during necropsy. The higher prevalence (63%) of otitis media in the retrospective postmortem study12 of rabbits with vestibular disease suggests the occurrence of false-negative results with radiography and CT, as reported for dogs with middle ear disease.25 The prevalence of CT-detected changes of the middle ear in the group 2 rabbits of the present study was 27%. Although this is within the reported prevalence range of 11.5% to 32%, all previous studies of the prevalence of subclinical middle ear disease were based on postmortem findings of meat rabbits1,8 or research rabbits.3,4 Computed tomography lesions of the middle ear in rabbits in the present study were similar to those described for dogs,25,34 cats,26 and other rabbits.7,27,28 A strong association was found between the occurrence of bulla lysis and clinical otitis media. This finding was different from a previous report26 for cats, in which CT findings of the tympanic bulla were similar among cases of clinical and subclinical middle ear disease. In addition, the rabbits in the present study had higher prevalences of increased CT attenuation within the middle ear and bulla lysis and a lower prevalence of increased bulla wall thickness, compared with cats with clinical middle ear disease.26 In cats, the presence of nasopharyngeal polyps can cause increased CT attenuation within the middle ear.35 Lysis of the tympanic bulla in dogs and cats occurs with severe middle ear infections, although neoplasia or cholesteatoma can cause similar lesions.20,36 Within the middle ear of rabbits, neoplasia, polyps, and cholesteatoma have not been reported.37 In the rabbits with clinical middle ear disease in the present study, an equal number of rabbits had unilateral and bilateral middle ear changes identified by CT. A higher prevalence (86%) of bilateral middle ear disease in rabbits with vestibular disease secondary to otitis media has been reported.12 For most rabbits with clinical middle ear disease in the present study, the body side with vestibular signs was consistent with the side of the CT-detected lesions in the middle or inner ear. In cases of bilateral disease, vestibular signs were ipsilateral to the more severely affected side. These results differ from those of a previous study in rabbits, in which clinical signs were not consistent with postmortem ear evaluation findings.12 Among the 11 rabbits with peripheral vestibular disease due to middle ear disease in the present study, 6 had no CT evidence of inner ear disease. For dogs and cats, the occurrence of peripheral vestibular signs implies the presence of
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evidenced by CT, in group 2 had no abnormal changes in the middle ear. In the present study, no significant association was found between upper respiratory tract disease and CT-detected changes of the middle ear in rabbits. This finding is different from those of previous reports1,4,8,10 of a strong association between otitis media and upper respiratory tract disease in rabbits. Middle ear changes without external ear changes were identified by CT in both groups of rabbits. In addition, all rabbits with subclinical middle ear disease with upper respiratory tract disease had bilateral changes. Although these findings might reflect otitis media secondary to inflammation of the auditory tube or translocation of flora from within the nasopharynx, other factors may play a role in the development of otitis media in rabbits with upper respiratory tract disease. These may include the type or pathogenicity of the bacteria colonizing the middle ear, host immunity, and concurrent diseases other than external ear disease and upper respiratory tract infection. The role of viruses, anaerobic bacteria, and fungi in the development of otitis media in rabbits remains unknown. In the present study, all rabbits with CT-detected changes of the middle ear had an increased CT attenuation within the tympanic cavity; thus, primary secretory otitis media, as described in Cavalier King Charles Spaniels,40 may play a role in the development of middle ear disease in rabbits. Allergic rhinitis, reported as a common cause of otitis media in children,41 has been anecdotally reported as a cause of otitis media in rabbits. Suppurative otitis media can be induced in rabbits by experimentally altering auditory tube function without the inoculation of bacteria; therefore, chronic inflammation associated with allergic rhinitis could initiate and maintain the hypersecretory state of the middle ear mucosa presumed to be responsible for chronic otitis media.42,43 An altered conformation of the skull described for some rabbit breeds, reported to predispose those rabbits to dental and nasolacrimal duct problems,44 may also predispose them to middle ear disease. This association is well described for humans with craniofacial malformations41 and for brachycephalic dogs.45 Additional studies are needed to investigate these proposed predisposing factors for middle ear disease in rabbits. Owing to the retrospective nature of the present study, inclusion criteria, and method of diagnosis (CT examination), the prevalence of clinical and subclinical middle ear disease determined in this study may not accurately reflect the overall prevalence of ear disease in domestic rabbits. A prospective study with broader inclusion criteria, a detailed client survey, additional diagnostic tests (including otoscopy with cytologic and microbiological evaluation of middle ear exudate samples, CT with contrast agent administration, and MRI), and comparison of images of middle ear changes with surgical and histopathologic findings would provide a better understanding of middle ear disease in pet rabbits. The intent of the present study was to describe the prevalence and characteristics of CT-detected changes of the middle ear in rabbits with and without signs consistent or suggestive of ear disease (ie, clinically and subclinically affected rabbits). Otitis media–related lesions were frequently detected by CT in rabbits with no signs of ear disease. Increased CT attenuation within the tympanic cavity was seen in all affected middle ears. Lysis of the tympanic bulla was more prevalent in clini342
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cal cases of middle ear disease and, although not significantly, was associated with progression of subclinical middle ear disease to vestibular disease. Otitis externa and ear conformation were shown to be important predisposing factors for the development of middle ear disease in rabbits. No strong association was found between the presence of middle ear disease and upper respiratory tract disease, with other factors likely playing a role in this mechanism of middle ear disease. Further studies are needed to investigate the pathophysiologic mechanisms of middle ear disease development and to determine the sensitivity and specificity of CT for the diagnosis of middle ear disease in rabbits. a. b. c. d. e.
Picker PQS, Picker International, Cleveland, Ohio. Toshiba Acquilion LB, Toshiba America Medical Systems Inc, Tustin, Calif. Carestream Vue PACS, Carestream Health Inc, Rochester, NY. Excel 2013, Microsoft Corp, Redmond, Wash. QuickCalcs: analyze a 2X2 contingency table, GraphPad Software Inc, La Jolla, Calif. Available at: graphpad.com/quickcalcs/ contingency1/. Accessed Apr 14, 2014.
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Flatt RE, Deyoung DW, Hogle RM. Suppurative otitis media in the rabbit: prevalence, pathology, and microbiology. Lab Anim Sci 1977;27:343–347. Oglesbee BL. Otitis media and interna. In: The 5-minute veterinary consult: ferret and rabbit. Ames, Iowa: Blackwell Publishing, 2006;311–313. Snyder SB, Fox JG, Soave OA. Subclinical otitis media associated with Pasteurella multocida infections in New Zealand white rabbits (Oryctolagus cuniculus). Lab Anim Sci 1973;23:270–272. Smith DT, Webster LT. Epidemiological studies on respiratory infections of the rabbit: VI. Etiology of otitis media. J Exp Med 1925;41:275–283. Varga M. Cardiorespiratory disease. In: Textbook of rabbit medicine. Woburn, Mass: Butterworth Heinemann Elsevier, 2002;324–334. Chow EP. Surgical management of rabbit ear disease. J Exot Pet Med 2011;20:182–187. Eatwell K, Mancinelli E, Hedley J, et al. Partial ear canal ablation and lateral bulla osteotomy in rabbits. J Small Anim Pract 2013;54:325–330. Deeb BJ, DiGiacomo RF, Bernard BL, et al. Pasteurella multocida and Bordetella bronchiseptica infections in rabbits. J Clin Microbiol 1990;28:70–75. Fox RR, Norberg RF, Myers DD. The relationship of Pasteurella multocida to otitis media in the domestic rabbit (Oryctolagus cuniculus). Lab Anim Sci 1971;21:45–48. Varga M. Neurological and locomotor disorders. In: Textbook of rabbit medicine. Woburn, Mass: Butterworth Heinemann Elsevier, 2002;307–323. Fisher P, Carpenter J. Rabbits: neurologic and musculoskeletal diseases. In: Quesenberry K, Carpenter J, eds. Ferrets, rabbits and rodents: clinical medicine and surgery. 3rd ed. St Louis: Elsevier, 2012;245–256. Kunstýr I, Naumann S. Head tilt in rabbits caused by pasteurellosis and encephalitozoonosis. Lab Anim 1985;19:208–213. Gruber A, Pakozdy A, Weissenbock H, et al. A retrospective study of neurological disease in 118 rabbits. J Comp Pathol 2009;140:31–37. Jeklova E, Jekl V, Kovarcik K, et al. Usefulness of detection of specific IgM and IgG antibodies for diagnosis of clinical encephalitozoonosis in pet rabbits. Vet Parasitol 2010;170:143–148. Oglesbee BL. Otitis externa and media. In: The 5-minute veterinary consult: ferret and rabbit. Ames, Iowa: Blackwell Publishing, 2006;308–310. Capello V. Surgical treatment of otitis externa and media in pet rabbits. Exot DVM 2004;6:15–21. Kangsanarak J, Navacharoen N, Fooanant S, et al. Intracranial JAVMA, Vol 246, No. 3, February 1, 2015
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three radiographic projections for detection of fluid in the rabbit tympanic bulla. Vet Radiol Ultrasound 2010;51:48–51. King AM, Posthumus J, Hammond G, et al. Comparison of ultrasonography, radiography and a single computed tomography slice for the identification of fluid within the tympanic bulla of rabbit cadavers. Vet J 2012;193:493–497. Love NE, Kramer RW, Spodnick GJ, et al. Radiographic and computed tomographic evaluation of otitis media in the dog. Vet Radiol Ultrasound 1995;36:375–379. Oliveira CR, O’Brien RT, Matheson JS, et al. Computed tomographic features of feline nasopharyngeal polyps. Vet Radiol Ultrasound 2012;53:406–411. Travetti O, Giudice C, Greci V, et al. Computed tomographic features of middle ear cholesteatoma in dogs. Vet Radiol Ultrasound 2010;51:374–379. King AM, Hall J, Cranfield F, et al. Anatomy and ultrasonographic appearance of the tympanic bulla and associated structures in the rabbit. Vet J 2007;173:512–521. Rossmeisl JH Jr. Vestibular disease in dogs and cats. Vet Clin North Am Small Anim Pract 2010;40:81–100. Harcourt-Brown F, Chitty J. Facial abscesses. In: HarcourtBrown F, Chitty J, eds. BSAVA manual of rabbit surgery, dentistry and imaging. Gloucester, England: British Small Animal Veterinary Association, 2013;395–428. Cole LK. Primary secretory otitis media in Cavalier King Charles Spaniels. Vet Clin North Am Small Anim Pract 2012;42:1137–1142. Sismanis A. Otitis media: the pathogenesis approach. Assessment and treatment of associated upper respiratory tract pathology. Otolaryngol Clin North Am 1991;24:947–955. Ovesen T, Paaske PB, Blegvad S, et al. Histological examination of the rabbit middle ear in secretory otitis media with and without a ventilation tube. APMIS 1992;100:839–844. Schousboe LP, Rasmussen LM, Ovesen T. Induction of mucin and adhesion molecules in middle ear mucosa. Acta Otolaryngol 2001;121:596–601. Meredith A. General biology and husbandry. In: Meredith A, Flecknell P, eds. BSAVA manual of rabbit medicine and surgery. 2nd ed. Gloucester, England: British Small Animal Veterinary Association, 2006;1–17. Owen MC, Lamb CR, Lu D, et al. Material in the middle ear of dogs having magnetic resonance imaging for investigation of neurologic signs. Vet Radiol Ultrasound 2004;45:149–155.
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complications of suppurative otitis media: 13 years’ experience. Am J Otol 1995;16:104–109. Sturges BK, Dickinson PJ, Kortz GD, et al. Clinical signs, magnetic resonance imaging features, and outcome after surgical and medical treatment of otogenic intracranial infection in 11 cats and 4 dogs. J Vet Intern Med 2006;20:648–656. Garosi LS, Dennis R, Schwarz T. Review of diagnostic imaging of ear diseases in the dog and cat. Vet Radiol Ultrasound 2003;44:137–146. Bischoff MG, Kneller SK. Diagnostic imaging of the canine and feline ear. Vet Clin North Am Small Anim Pract 2004;34:437–458. Doust R, King A, Hammond G, et al. Assessment of middle ear disease in the dog: a comparison of diagnostic imaging modalities. J Small Anim Pract 2007;48:188–192. Knipe MF. Principles of neurological imaging of exotic animal species. Vet Clin North Am Exot Anim Pract 2007;10:893–907. Van Caelenberg AI, De Rycke LM, Hermans K, et al. Computed tomography and cross-sectional anatomy of the head in healthy rabbits. Am J Vet Res 2010;71:293–303. Keeble E. Common neurological and musculoskeletal problems in rabbits. In Pract 2006;28:212–218. Rohleder JJ, Jones JC, Duncan RB, et al. Comparative performance of radiography and computed tomography in the diagnosis of middle ear disease in 31 dogs. Vet Radiol Ultrasound 2006;47:45–52. Shanaman M, Seiler G, Holt DE. Prevalence of clinical and subclinical middle ear disease in cats undergoing computed tomographic scans of the head. Vet Radiol Ultrasound 2012;53:76–79. Stieve-Caldwell EL, Morandi F, Souza M, et al. What is your diagnosis? J Am Vet Med Assoc 2009;235:665–666. Veraa S, Schoemaker NJ. CT and MRI scanning and interpretation. In: Harcourt-Brown F, Chitty J, eds. BSAVA manual of rabbit surgery, dentistry and imaging. Gloucester, England: British Small Animal Veterinary Association, 2013;107–114. DiGiacomo RF, Garlinghouse LE Jr, Van Hoosier GL Jr. Natural history of infection with Pasteurella multocida in rabbits. J Am Vet Med Assoc 1983;183:1172–1175. Kumar B, Rajashekar G, Rao P. Vestibular syndrome in a rabbit. Indian Vet J 2000;77:268–269. Bjotvedt G, Geib LW. Otitis media associated with Staphylococcus epidermidis and Psoroptes cuniculi in a rabbit. Vet Med Small Anim Clin 1981;76:1015–1016. Hammond G, Sullivan M, Posthumus J, et al. Assessment of
Computed tomographic features of clinical and subclinical middle ear disease in domestic rabbits (Oryctolagus cuniculus): 88 cases (2007–2014) Ricardo de Matos, LMV; Jennifer Ruby, DVM; Ruth A. Van Hatten, DVM; Margret Thompson, DVM Objective—To describe and compare CT abnormalities of the middle ear in rabbits (Oryctolagus cuniculus) that had clinical or subclinical middle ear disease and to determine the prevalence of otitis media and evaluate the role of predisposing factors for otitis media in that species. Design—Retrospective case series. Animals—88 domestic rabbits. Procedures—Medical records for rabbits that underwent CT of the head in June 2007 through February 2014 were searched and classified on the basis of reason for head CT (ie, ear-related disease vs non–ear-related disease). The ears, upper respiratory tract, teeth, and other important structures of each rabbit’s head were evaluated. Follow-up information was obtained for rabbits with CT abnormalities of the middle ear without clinical signs (ie, subclinical disease). Results—12 of 21 (57%) rabbits with clinical signs of ear disease and 18 of 67 (27%) rabbits without clinical signs of ear disease had CT abnormalities of the middle ear. In CT images, all affected ears had soft tissue–attenuating material within the tympanic bulla. Tympanic bulla lysis was associated with clinical middle ear disease. Most (12/18) rabbits with subclinical middle ear disease remained subclinical after CT examination. Middle ear CT-detected changes and lop-ear conformation or otitis externa were strongly correlated; middle ear disease and upper respiratory tract disease were not correlated. Conclusions and Clinical Relevance—Data suggested that subclinical otitis media frequently affects rabbits, and those with bulla lysis should be closely monitored. Lop-eared rabbits and rabbits with otitis externa had a higher risk of developing otitis media. (J Am Vet Med Assoc 2015;246:336–343)
O
titis media, or inflammatory disease of the middle ear, in rabbits is commonly reported.1–3 Otitis media can be difficult to diagnose in live rabbits because those with otitis media are often subclinically affected unless the disease is associated with otitis externa or interna.1,3–7 Postmortem studies1,4 investigating subclinical otitis media in rabbits have indicated prevalences ranging from 11.5%8 to 32%. With otitis interna, rabbits develop signs of vestibular disease.4,9–12 Reports vary with respect to the prevalence of otitis media in rabbits with vestibular disease: 5.5% in a postmortem study13 of rabbits with neurologic disease, 24% in an Encephalitozoon cuniculi seroprevalence study,14 and 63% in a postmortem study12 of rabbits with vestibular disease. Most of these studies determined prevalence of subclinical and clinical middle ear disease in rabbits at necropsy, not on an antemortem basis, and in meat rabbits or research rabbits, not in domestic rabbits. Examination of the external ear canal and tympanic membrane has been proposed for diagnosis of subclinical otitis media. However, neither an apparently normal tympanic membrane nor an apparently normal external ear canal excludes the presence of otitis media.1,4,15 In adFrom the Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853. Address correspondence to Dr. de Matos ([email protected]). 336
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dition, examination of the tympanic membrane can be challenging, especially in rabbits with otitis externa and in lop-eared rabbits.6,16 Early diagnosis of otitis media is extremely important because infection can spread to the inner ear (causing vestibular disease due to labyrinthitis) or through the internal acoustic meatus and along the vestibulocochlear nerve to the brain (resulting in severe neurologic signs due to encephalomyelitis).4,9–13 Rabbits with otitis interna develop clinical signs of peripheral vestibular disease, including head tilt, nystagmus, ataxia, or rolling.2 Facial nerve paralysis and Horner’s syndrome can also develop with otitis media or interna in rabbits.2 Otogenic intracranial infection in humans17 and in dogs and cats18 is reported to be rare. However, it is relatively common in rabbits, affecting up to 50% of rabbits with otitis media.12,13 In those cases, clinical signs of central vestibular disease may be preceded by signs of peripheral vestibular disease, making distinction between central and peripheral vestibular diseases difficult.10,18 The main differential diagnosis for rabbits with central vestibular signs is E cuniculi infection.10–13 Even though serologic tests are available for anti–Pasteurella multocida and anti– E cuniculi antibodies, positive results of assays for serum antibodies reflect exposure and do not correlate with active disease caused by either organism.10,11,13 Owing to the often subclinical signs of otitis media, the difficulty in differentiating otitis media or interna JAVMA, Vol 246, No. 3, February 1, 2015
Materials and Methods Case selection—The medical records for rabbits that were evaluated at the Cornell University Hospital for Animals from June 2007 to February 2014 were searched for those that underwent CT of the head. Information collected from each medical record included age, weight, sex, ear conformation, past medical history, reason for visit, and physical examination findings. Rabbits that underwent head CT were assigned to 1 of 2 groups according to the reason for their visit. Group 1 included rabbits evaluated because of clinical signs of otitis externa (head JAVMA, Vol 246, No. 3, February 1, 2015
shaking, pinnal pruritus, malodorous ears, or, for rabbits with upright ears, holding the affected ears down) or middle ear disease (signs of vestibular disease or facial nerve paralysis). Group 2 included rabbits evaluated for conditions not related to ear disease (dental disease, upper respiratory tract disease, and other conditions of the head region, such as ocular or periocular disease or soft tissue or bone masses). CT examinations—All head CT examinations were performed after each rabbit was sedated with ketamine (10 mg/kg [4.5 mg/lb]) and diazepam (0.5 mg/kg [0.23 mg/lb], IV) or anesthetized with isoflurane with oxygen delivered via face mask. Computed tomographic scans were obtained with a single-slice axial CT unita (for cases examined between August 2008 and July 2009) or a 16-slice helical CT unitb (for cases examined between August 2009 and March 2014). Images were acquired in 0.5- to 1-mm contiguous transverse slices (120 kVp; mAs set automatically) with rabbits positioned in ventral recumbency. Most scans were performed with a soft tissue and bone algorithm (72/88 rabbits), with a few performed with a bone algorithm only (15/88 rabbits) or a soft tissue algorithm only (1/88 rabbits). Image evaluation—External, middle, and inner portions of the ear were evaluated for each rabbit by a board-certified radiologist (MT) and a radiology resident (RAVH). Image evaluation was performed in chronological order of CT examinations. Reviewers were blinded to the rabbit’s group assignment, the reason for head CT, and the other reviewer’s interpretation of ear CT-detected changes. Once the image review process was completed, inter-reviewer discrepancies were addressed with collaborative image evaluation during which both reviewers agreed on a single diagnosis. Images were interpreted on a commercial picture archiving and communication systemc with multiple planes and windows available. The external ear was evaluated for increased attenuation within the canal, thickness of the wall of the external ear canal, mineralization of the auricular cartilages, and presence of a mass or masses within or associated with the external ear canal. The middle ear was evaluated for the presence of attenuating material within the tympanic cavity or increased thickness, irregularity, expansion, or lysis of the tympanic cavity wall. The inner ear was evaluated for sclerosis or lysis of the petrous temporal bone or loss of cochlear semicircular canal definition. Lesions of the external, middle, and inner ear were categorized as absent or present on CT images. In addition, abnormalities in the upper respiratory tract and teeth and other remarkable findings within the head region were recorded. Follow-up—Information regarding the progression of subclinical middle ear disease in affected rabbits was obtained by follow-up visits or telephone or email contact with the owners or referring veterinarians. When available, findings of a follow-up CT ear examination were also recorded, characterized, and compared with the initial CT findings. Data analysis—Descriptive statistics were used for data analysis and calculated in spreadsheet softwared (numeric data) and an online data analysis programe Scientific Reports
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from central vestibular disease, and the relatively high prevalence of otogenic intracranial infection, diagnostic imaging is important for evaluation of the middle ear and early identification of middle ear disease in rabbits. Computed tomography allows cross-sectional evaluation of the entire head, including teeth and upper respiratory tract, without superimposition of structures.19–24 Computed tomography is reported to be more sensitive than, and as specific as, radiography for diagnosing and characterizing the severity of middle ear disease in dogs.25 Computed tomographic findings of otitis media in dogs and cats include thickening, irregularity, proliferation, or lysis of the tympanic bulla wall. In addition, a fluid or soft tissue density may be evident within the lumen of the bulla.19,20,26 The use of CT for diagnosis of otitis media in rabbits has been described in the veterinary medical literature.6,7,11,24,27,28 However, the information is descriptive and limited to CT-detected changes in clinical cases of otitis media. In rabbits with otitis media, the primary infection is believed to be a result of bacteria within the nasopharynx that reach the middle ear via the auditory tube.1,4,10 This pathogenesis is supported by the fact that most infections are caused by P multocida, a respiratory tract pathogen.1,3,4,8,9,11,12,29 In addition, high prevalences of middle ear disease in rabbits with concurrent upper respiratory tract infections have been reported (78%4 and 85%8). Otitis media also develops secondary to bacterial or parasitic otitis externa.1,15,30,31 Otitis externa develops more commonly in lop-eared rabbits, possibly because of abnormal conformation of the external ear canal.15 The purpose of the study reported here was to describe and compare CT abnormalities in the middle ear of domestic rabbits (Oryctolagus cuniculus) that had clinical middle ear disease with those in rabbits without signs of disease (subclinical disease) and to determine the prevalence of otitis media in that species. Because there are multiple possible causes of otitis media in rabbits that are not fully understood, another aim was to evaluate the frequency of proposed predisposing factors of otitis media (upper respiratory tract disease, otitis externa, and lop-ear conformation) in rabbits with subclinical or clinical otitis media and in rabbits with or without otitis media. We hypothesized that CT signs of otitis media are a common finding in rabbits that undergo head CT for reasons other than ear disease, that CT middle ear abnormalities would differ between rabbits with clinical and subclinical otitis media, and that predisposing factors to otitis media would be detected more commonly in rabbits with clinical and subclinical otitis media than in rabbits without otitis media.
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(categorical data). Numeric data (age and weight) were described as mean ± SD. Categorical data (presence or absence of CT-detected changes of the external, middle, or inner ear; unilateral or bilateral disease; type of lesion present in the middle ear; ear conformation; and upper respiratory tract disease) were described as the frequency of occurrence of each category by group. Depending on sample size, Fisher exact tests or χ2 tests were used to determine the association between the type of CT middle ear lesion and reason for visit (groups 1 and 2) and, within group 2, between rabbits with permanent and temporary subclinical middle ear disease. These same tests were used to determine the association between middle ear disease (clinical vs subclinical and presence vs absence) and the proposed middle ear predisposing factors (lop-ear conformation, otitis externa, and upper respiratory tract disease). Values of P < 0.05 were considered significant. Results Case selection—Eighty-eight of 784 rabbits evaluated from June 2007 to February 2014 met the inclusion criteria. Twenty-one (24%) rabbits were evaluated because of ear disease or signs suggestive of ear disease (group 1). Clinical signs in group 1 included clinical otitis externa (n = 6), facial nerve paralysis (3), and signs of vestibular disease (20). The group included 9 (43%) males and 12 (57%) females. These rabbits had a mean ± SD age of 4.4 ± 2.6 years (range, 0.1 to 8 years) and mean weight of 1.9 ± 0.92 kg (4.2 ± 2.0 lb; range, 0.6 to 4.9 kg [1.3 to 10.8 lb]). Sixty-seven (76%) rabbits included in the study were evaluated because of other conditions not related to or suggestive of ear disease (group 2). Clinical problems in group 2 included dental disease (n = 33), upper respiratory tract disease (18), and other conditions involving the skull or head (16). Group 2 included 47 (70%) males and 20 (30%) females. Rabbits in group 2 had a mean age of 4.9 ± 2.51 years (range, 0.2 to 11.6 years) and mean weight of 2.26 ± 0.9 kg (5.0 ± 2.0 lb; range, 0.7 to 5.3 kg [1.5 to 11.7 lb]). Prevalence of CT-detected middle ear changes— Twelve of the 21 (57%) rabbits in group 1 had CT abnormalities of the middle ear (Table 1). Among the 20
rabbits with signs of vestibular disease in group 1, 11 (55%) had CT-detected changes consistent with middle ear disease; the other 9 (45%) had no CT-detected changes in the external, middle, or inner ears, and presumptive central vestibular disease was diagnosed. Eighteen of the 67 (27%) rabbits in group 2 had CT abnormalities of the middle ear. Characterization of CT abnormalities of the middle ear—For group 1 rabbits with CT-detected changes of the middle ear, 6 had unilateral changes and 6 had bilateral changes (overall, 18 affected ears; Table 1). All those affected ears had soft tissue attenuating material (ie, increased attenuation) within the tympanic bulla; of the 18 ears, 10 had lysis of the bulla (prevalence, 55%) and 3 had thick tympanic bulla (Figure 1). The 3 rabbits in group 1 with facial nerve paralysis had CTdetected changes of the middle ear. One rabbit had middle ear changes ipsilateral to facial nerve paralysis and no vestibular signs. The other 2 rabbits had bilateral middle ear changes as well as head tilt and facial nerve paralysis ipsilateral to inner ear CT-detected changes. The type and severity of middle ear CT-detected changes in rabbits with facial nerve paralysis were similar to the findings for other rabbits in group 1 that had signs of vestibular disease without facial nerve paralysis. Five of the group 1 rabbits with signs of vestibular disease and CT-detected changes of the middle ear had unilateral disease and ipsilateral vestibular signs. The remaining 6 rabbits with signs of vestibular disease and CT-detected changes of the middle ear had bilateral middle ear disease. Vestibular signs were ipsilateral to the ear with more severe middle ear CT lesions (2 cases) or to the ear with inner ear changes detected with CT (2 cases). The 2 remaining rabbits with vestibular signs had bilateral middle and inner ear disease. Despite similar CT abnormalities and severity of disease for both middle and inner ears, those rabbits had unilateral vestibular signs. Among the 18 group 2 rabbits with CT evidence of middle ear disease (ie, relevant CT abnormalities) but no clinical signs, 10 had unilateral subclinical disease and 8 had bilateral subclinical disease (overall, 26 affected ears; Table 1). All affected middle ears of rab-
Table 1—Prevalence of middle, external, and inner ear CT-detected changes in 88 domestic rabbits (Oryctolagus cuniculus) that had clinical middle ear disease and those without signs of middle ear disease (subclinical disease). Rabbits with subclinical disease Rabbits with clinical disease
Variable
All
Rabbits with upper respiratory tract disease
33/67
Rabbits with other problems
Total No. of rabbits
21/88
67/88
No. of rabbits with CT-detected middle ear changes (%) No. of rabbits unilaterally affected (%) No. of rabbits bilaterally affected (%)
12/21 (57) 6/12 (50) 6/12 (50)
18/67 (27) 10/18 (56) 8/18 (44)
7/18 (39) 0/7 (0) 7/7 (100)
8/33 (24) 7/8 (88) 1/8 (13)
3/16 (19) 3/3 (100) 0/3 (0)
No. of rabbits with CT-detected external ear changes (%) No. of rabbits unilaterally affected (%) No. of rabbits bilaterally affected (%)
10/21 (48) 2/10 (20) 8/10 (80)
32/67 (48) 3/32 (9) 29/32 (91)
11/18 (61) 0/11 (0) 11/11 (100)
15/33 (45) 1/15 (7) 14/15 (93)
6/16 (38) 2/6 (33) 4/6 (67)
4/21(19) 2/4 (50) 2/4 (50)
2/67 (3) 2/2 (100) 0/2 (0)
1/18 (6) 1/1 (100) 0/1 (0)
1/33 (3) 1/1 (100) 0/1 (0)
0/16 (0) NA NA
No. of rabbits with CT-detected inner ear changes (%) No. of rabbits unilaterally affected (%) No. of rabbits bilaterally affected (%)
18/67
Rabbits with dental disease
16/67
NA = Not applicable. 338
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the head was repeated for evaluation of chronic upper respiratory tract disease, and no progression of middle ear lesions was detected (Figure 3). On comparison of middle ear CT lesions between group 2 rabbits that remained subclinical and rabbits that eventually developed clinical signs of middle ear disease, the prevalence of attenuation and thickening of the tympanic bulla was similar. However, rabbits that eventually developed clinical signs had a higher prevalence of bulla lysis, compared with rabbits that remained subclinically affected (3/5 vs 1/10). Nevertheless, the difference in prevalence of lytic changes of the bulla between these 2 subgroups was not significant (P = 0.262). The presence of CT-detected changes of the external and inner portion of the ear was also recorded for rabbits in both groups (Table 1). Four rabbits in group 1 had CTdetected changes in all 3 portions of the ear (external, middle, and inner ear). Both group 2 rabbits with inner ear CT-detected changes had no vestibular signs before or at the time of CT examination. One rabFigure 1—Transverse (A and C) and dorsal (B) CT images at the level of the tympanic bit remained subclinical for 4 months after bullae of a 7-year-old spayed female lop-eared rabbit (Oryctolagus cuniculus) that had sudden-onset right head tilt and mild right facial nerve paralysis. The images are dis- CT (but was euthanized by IV injection of played in a bone (A and B) or soft tissue (C) algorithm and were obtained in 1-mm pentobarbital sodium solution because of contiguous slices. Both external ear canals are expanded with a soft tissue–attenuat- progression of dental disease). The other ing material. The left external ear canal is replaced by a large soft tissue–attenuating rabbit developed vestibular signs ipsilateral mass that expands from the left middle ear, causing local disruption and lysis of the left tympanic bulla and left inner ear. The right tympanic bulla is filled with soft tissue– to the affected inner ear 3 days after the CT attenuating material, but the normal structure of the bulla is maintained, and lysis of examination. These signs resolved within the petrous temporal bone is not detected. R = Right. 2 days, during which time antimicrobial treatment for an upper respiratory tract infection was administered. Two years later, the rabbit conbits in group 2 had increased attenuation within the tinued to have no recurrence of vestibular signs. tympanic cavity. The prevalence of bulla lysis was 19% (5/26), and that of increased bulla thickness was 19% Predisposing factors for middle ear disease—Of (5/26). Comparing the prevalence of CT-detected midthe 21 rabbits in group 1, 9 (43%) were lop-eared rabdle ear changes between the 2 groups, the prevalence bits. Of the 12 rabbits in group 1 with CT-detected of bulla lysis in rabbits with clinical middle ear disease middle ear changes, 9 had lop ears and 3 had upright (group 1) was significantly (P < 0.001) higher. ears. All rabbits with presumptive central vestibular One rabbit with subclinical middle ear CT disease disease had upright ears. For group 2, the distribution was euthanized by IV injection of pentobarbital sodium of lop-eared rabbits (28/67 [42%]) was similar to that solution during the CT examination because of advanced in group 1. Of the 18 rabbits with CT-detected changes dental disease. Follow-up information was available for of the middle ear in group 2, 12 had lop ears and 6 had all other rabbits with subclinical middle ear disease, with upright ears. Combining rabbits with clinical or suba median monitoring time after CT examination of 23 clinical middle ear disease (30 rabbits), 21 (70%) had months (range, 2 months to 5 years). Five of 17 group 2 lop ears and 9 (30%) had upright ears. For the 58 rabrabbits with CT abnormalities of the middle ear eventubits with no CT-detected middle ear changes, 16 (28%) ally developed temporary (n = 2) or persistent (3) signs had lop ears and 42 (72%) had upright ears. Although of peripheral vestibular disease after CT (median interthere was no association between ear position and clinival after CT examination, 10 months [range, 3 days to 2 cal or subclinical ear disease, there was a significant (P years]). A CT scan of the head was repeated in 2 of the < 0.001) association between lop ears and presence of rabbits that developed persistent vestibular signs, and CT-detected changes of the middle ear. The study data images confirmed the progression of middle ear disease indicated a significant association between upright ears in comparison with the initial CT findings (Figure 2). and presumptive central vestibular disease. The remaining 12 rabbits with CT abnormalities of the Of the 12 rabbits in group 1 with CT-detected changmiddle ear but no signs of middle ear disease did not es of the middle ear, 10 also had CT abnormalities of the develop signs suggestive of ear disease after CT examinaexternal ear; 2 had only middle ear changes. No rabbits in tion (median interval after CT examination, 9 months this group had CT-detected changes limited to the exter[range, 2 months to 5 years]). For 2 of the rabbits that nal ear. For group 2, 15 of the 18 rabbits with CT-detected remained subclinically affected, CT examination of
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Figure 2—Transverse CT images (obtained over a period of 13 months) at the level of the tympanic bullae of a 2-year-old sexually intact male Miniature Rex rabbit with chronic upper respiratory tract infection. A—The image is displayed in a bone algorithm; images were obtained in 1-mm contiguous slices at the initial evaluation. Bilateral otitis media is evident with both bullae occupied by a soft tissue– attenuating material and lysis present at the lateral aspect of the right tympanic bulla. The inner ears are unaffected. B—Image obtained 10 months later when the rabbit was evaluated because of a right head tilt and worsening upper respiratory infection. The bilateral otitis media has advanced to include expansile lytic lesions along both tympanic bullae, with the right being more severely affected than the left. The inner ears remain unaffected. C—Image obtained 13 months after the first CT examination when the rabbit developed neurologic clinical signs after discontinuing medications. The bilateral otitis media remains severe as before. There is a new development of lysis of the left inner ear; however, the right inner ear remains unaffected. R = Right.
upper respiratory tract disease and had CT abnormalities of the upper respiratory tract. For group 2 rabbits, prevalences of middle ear disease by reason for head CT were summarized (Table 1). Rabbits with signs of upper respiratory tract disease had a higher prevalence of CT-detected changes of the middle ear, with all rabbits having bilateral disease. However, the difference in prevalence of CT changes of the middle ear with regard to the different reasons for head CT in group 2 rabbits was not significant. Combining rabbits with subclinical Figure 3—Transverse CT images at the level of the tympanic bullae of a 2-year-old and clinical middle ear disease (30 cases), castrated male Miniature Holland Lop rabbit with chronic upper respiratory tract disease and mild left facial nerve paralysis. The images are displayed in a bone algorithm 10 (33%) had CT-detected changes conand were obtained in 1-mm contiguous slices. A—Both tympanic bullae are occupied sistent with upper respiratory tract disby a soft tissue–attenuating material, and both inner ears appear intact. Additional ease or a history of upper respiratory tract images in the CT scan revealed severe, destructive rhinopathy on the right (image not shown). B—Image obtained from same rabbit in panel A 2 years later to evaluate the disease, and 20 (67%) had neither CTchronic upper respiratory tract disease. The bilateral otitis externa and media are un- detected changes within the upper respichanged, and the destructive rhinopathy is progressive (image not shown). R = Right. ratory tract nor a history of upper respiratory tract disease. Among the 58 rabbits with no middle ear changes identified by CT, 20 (34%) middle ear lesions had CT-detected abnormalities of the had CT-detected changes consistent with upper respiraexternal ear, with 3 having only middle ear changes. In tory tract disease or a history of upper respiratory tract contrast, 17 of 32 (53%) rabbits with CT-detected external disease, and 38 (66%) had neither CT-detected changes ear lesions had no CT-detected lesions in the middle ears. within the upper respiratory tract nor a history of upper None of these rabbits developed signs of otitis externa, respiratory tract disease. There was no significant (P = media, or interna following CT examination. Combining 0.88) association between upper respiratory tract disease rabbits with subclinical and clinical middle ear disease (30 and presence of middle ear CT abnormalities. cases), 25 (83%) rabbits had CT-detected changes in the In group 2, 12 rabbits had CT-detected changes of the external ear, and 5 (17%) had apparently normal extermiddle ear, and their disease remained subclinical, and 5 nal ears. For rabbits with no middle ear CT abnormalirabbits with subclinical disease eventually developed vesties (n = 58), 17 (29%) rabbits had CT-detected changes tibular signs. Analysis of those data revealed no significant in the external ear, and 41 (71%) had apparently normal association between progression of disease and ear position, external ears. Although the prevalence of otitis externa in presence of external ear disease, or reason for head CT. groups 1 and 2 was the same, there was a significant (P < 0.001) association between otitis externa and presence of CT-detected changes of the middle ear. Discussion Only 3 of 12 rabbits in group 1 with CT-detected The overall prevalence of clinical middle ear dischanges of the middle ear had a history of upper respiratory ease in rabbits in this retrospective study was 57%. For tract disease (2 rabbits) or had CT abnormalities of the uprabbits with vestibular signs, the prevalence was 55%. per respiratory tract (1 rabbit). For group 2, 7 of 18 rabbits Different prevalences (5.5%,13 24%,14 and 63%12) of with CT-detected changes of the middle ear had a history of 340
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inner ear disease.38 It is possible that changes in the inner ear of these rabbits were subtle or limited to the soft tissue portion, which would be more readily detected by CT with contrast agent administration or MRI.20,28 In the present study, there was no association between the characteristics of the CT-detected middle ear changes and the occurrence of facial nerve paralysis. Facial nerve paralysis is not specific to ear disease and can develop in rabbits with abscesses or other masses in the nerve pathway.39 For rabbits with subclinical middle ear disease (group 2) in the present study, unilateral middle ear changes were more prevalent than bilateral middle ear changes (56% vs 44%). Previous reports describe a higher prevalence of bilateral subclinical otitis media in meat (70%1) and research (81%3) rabbits. As for other findings, discrepancies in these prevalences may be due to differences in rabbit populations, medical history, or method of diagnosis of otitis media. Two rabbits in group 2 had unilateral CT-detected changes of the inner ear and no vestibular signs before CT examination. In contrast, all rabbits in group 1 with CT-detected changes of the inner ear had persistent vestibular signs. Although it is possible that changes in the inner ear of the group 2 rabbits were limited to the bone structures of the inner ear, CT with contrast agent administration or MRI would have been helpful to more accurately evaluate the soft tissue portion of the inner ear and compare clinical and subclinical inner ear disease.28 The clinical relevance of CT abnormalities of the middle ear in rabbits with subclinical disease remains unknown. Seventy-one percent of rabbits with CTdetected changes of the middle ear remained subclinically affected after the CT examination in the present study. The reason for head CT, ear position, or presence of CT-detected external ear lesions was not associated with progression of subclinical ear disease. Rabbits with subclinical middle ear disease that eventually developed vestibular signs had a higher prevalence of bulla lysis, compared with rabbits that remained subclinically affected. Although the association was not significant (perhaps because of the small sample size), the authors recommend close monitoring (including CT examination) of rabbits with subclinical middle ear disease that have lysis of the tympanic bulla revealed by CT. Three proposed predisposing factors for the development of middle ear disease in rabbits were investigated in the present study: ear position, otitis externa, and upper respiratory tract disease. No significant association was found between ear position and the development of clinical or subclinical middle ear disease. However, the study results supported an association between CT-detected middle ear changes and lop-ear conformation and between central vestibular disease and upright-ear conformation. Similarly, a strong association was evident between external ear and middle ear changes identified by CT. It is unknown whether CT-detected changes within the external ear in rabbits with CT-detected lesions in the middle ear were a cause or consequence of middle ear disease in the rabbits in group 1. It is important to note that no rabbits in group 1 had CT-detected changes of the external ear alone, and 17 of 32 (53%) rabbits with external ear disease, as Scientific Reports
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clinical middle ear disease in rabbits have been previously reported. Among the various studies, these discrepancies are likely attributable to differences in rabbit populations, inclusion criteria, or method of diagnosis of otitis media. For the study14 that found a prevalence of 24%, diagnosis was based on otoscopic examination findings and radiographic abnormalities. The higher prevalence of middle ear disease reported in the present retrospective study could be due to the increased sensitivity and accuracy of CT for identifying changes of the middle ear, compared with routine radiography, as previously reported.25,32,33 One limitation of the present study and the one by Jeklova et al14 was that the imaging abnormalities of the middle ear were not confirmed during surgery, by histologic evaluation, or during necropsy. The higher prevalence (63%) of otitis media in the retrospective postmortem study12 of rabbits with vestibular disease suggests the occurrence of false-negative results with radiography and CT, as reported for dogs with middle ear disease.25 The prevalence of CT-detected changes of the middle ear in the group 2 rabbits of the present study was 27%. Although this is within the reported prevalence range of 11.5% to 32%, all previous studies of the prevalence of subclinical middle ear disease were based on postmortem findings of meat rabbits1,8 or research rabbits.3,4 Computed tomography lesions of the middle ear in rabbits in the present study were similar to those described for dogs,25,34 cats,26 and other rabbits.7,27,28 A strong association was found between the occurrence of bulla lysis and clinical otitis media. This finding was different from a previous report26 for cats, in which CT findings of the tympanic bulla were similar among cases of clinical and subclinical middle ear disease. In addition, the rabbits in the present study had higher prevalences of increased CT attenuation within the middle ear and bulla lysis and a lower prevalence of increased bulla wall thickness, compared with cats with clinical middle ear disease.26 In cats, the presence of nasopharyngeal polyps can cause increased CT attenuation within the middle ear.35 Lysis of the tympanic bulla in dogs and cats occurs with severe middle ear infections, although neoplasia or cholesteatoma can cause similar lesions.20,36 Within the middle ear of rabbits, neoplasia, polyps, and cholesteatoma have not been reported.37 In the rabbits with clinical middle ear disease in the present study, an equal number of rabbits had unilateral and bilateral middle ear changes identified by CT. A higher prevalence (86%) of bilateral middle ear disease in rabbits with vestibular disease secondary to otitis media has been reported.12 For most rabbits with clinical middle ear disease in the present study, the body side with vestibular signs was consistent with the side of the CT-detected lesions in the middle or inner ear. In cases of bilateral disease, vestibular signs were ipsilateral to the more severely affected side. These results differ from those of a previous study in rabbits, in which clinical signs were not consistent with postmortem ear evaluation findings.12 Among the 11 rabbits with peripheral vestibular disease due to middle ear disease in the present study, 6 had no CT evidence of inner ear disease. For dogs and cats, the occurrence of peripheral vestibular signs implies the presence of
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evidenced by CT, in group 2 had no abnormal changes in the middle ear. In the present study, no significant association was found between upper respiratory tract disease and CT-detected changes of the middle ear in rabbits. This finding is different from those of previous reports1,4,8,10 of a strong association between otitis media and upper respiratory tract disease in rabbits. Middle ear changes without external ear changes were identified by CT in both groups of rabbits. In addition, all rabbits with subclinical middle ear disease with upper respiratory tract disease had bilateral changes. Although these findings might reflect otitis media secondary to inflammation of the auditory tube or translocation of flora from within the nasopharynx, other factors may play a role in the development of otitis media in rabbits with upper respiratory tract disease. These may include the type or pathogenicity of the bacteria colonizing the middle ear, host immunity, and concurrent diseases other than external ear disease and upper respiratory tract infection. The role of viruses, anaerobic bacteria, and fungi in the development of otitis media in rabbits remains unknown. In the present study, all rabbits with CT-detected changes of the middle ear had an increased CT attenuation within the tympanic cavity; thus, primary secretory otitis media, as described in Cavalier King Charles Spaniels,40 may play a role in the development of middle ear disease in rabbits. Allergic rhinitis, reported as a common cause of otitis media in children,41 has been anecdotally reported as a cause of otitis media in rabbits. Suppurative otitis media can be induced in rabbits by experimentally altering auditory tube function without the inoculation of bacteria; therefore, chronic inflammation associated with allergic rhinitis could initiate and maintain the hypersecretory state of the middle ear mucosa presumed to be responsible for chronic otitis media.42,43 An altered conformation of the skull described for some rabbit breeds, reported to predispose those rabbits to dental and nasolacrimal duct problems,44 may also predispose them to middle ear disease. This association is well described for humans with craniofacial malformations41 and for brachycephalic dogs.45 Additional studies are needed to investigate these proposed predisposing factors for middle ear disease in rabbits. Owing to the retrospective nature of the present study, inclusion criteria, and method of diagnosis (CT examination), the prevalence of clinical and subclinical middle ear disease determined in this study may not accurately reflect the overall prevalence of ear disease in domestic rabbits. A prospective study with broader inclusion criteria, a detailed client survey, additional diagnostic tests (including otoscopy with cytologic and microbiological evaluation of middle ear exudate samples, CT with contrast agent administration, and MRI), and comparison of images of middle ear changes with surgical and histopathologic findings would provide a better understanding of middle ear disease in pet rabbits. The intent of the present study was to describe the prevalence and characteristics of CT-detected changes of the middle ear in rabbits with and without signs consistent or suggestive of ear disease (ie, clinically and subclinically affected rabbits). Otitis media–related lesions were frequently detected by CT in rabbits with no signs of ear disease. Increased CT attenuation within the tympanic cavity was seen in all affected middle ears. Lysis of the tympanic bulla was more prevalent in clini342
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cal cases of middle ear disease and, although not significantly, was associated with progression of subclinical middle ear disease to vestibular disease. Otitis externa and ear conformation were shown to be important predisposing factors for the development of middle ear disease in rabbits. No strong association was found between the presence of middle ear disease and upper respiratory tract disease, with other factors likely playing a role in this mechanism of middle ear disease. Further studies are needed to investigate the pathophysiologic mechanisms of middle ear disease development and to determine the sensitivity and specificity of CT for the diagnosis of middle ear disease in rabbits. a. b. c. d. e.
Picker PQS, Picker International, Cleveland, Ohio. Toshiba Acquilion LB, Toshiba America Medical Systems Inc, Tustin, Calif. Carestream Vue PACS, Carestream Health Inc, Rochester, NY. Excel 2013, Microsoft Corp, Redmond, Wash. QuickCalcs: analyze a 2X2 contingency table, GraphPad Software Inc, La Jolla, Calif. Available at: graphpad.com/quickcalcs/ contingency1/. Accessed Apr 14, 2014.
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