One of the more common abnormal presentations of disease in rabbits is a head tilt, which is often accompanied by nystagmus and circling.
One of the more common abnormal presentations of disease in rabbits is a head tilt, which is often accompanied by nystagmus and circling. As in dogs, there may be multiple etiologies for head tilts. The etiology may be neurologic or vestibular, and it may be difficult to differentiate between these. This presentation is designed to aid the practitioner in differentiating neurologic from vestibular head tilts, as well as identifying and treating the more common etiologies.
When considering head tilts in rabbits, the most common differentials are Encephalitozoon cuniculi and otitis media/interna. However, central nervous system infection or abscess, or a neoplastic process, must also be considered. There are other etiologies such as toxoplasmosis or baylisascaris, but these are rare and often diagnosis is made post-mortem. In this section we will emphasize diagnosis and treatment of otitis, as well as differentiating otitis from central nervous system disease. Encephalitozoon cuniculi will be discussed in a separate section.
Rabbits with central nervous system disease will have signs in addition to the head tilt. These may include changes in mentation, proprioceptive deficits, gait abnormalities, abnormalities in reflexes, cranial nerve deficits, and ataxia in addition to the head tilt or head turn. With otitis, the lesion is peripheral. With peripheral lesions, the head tilt is always towards the side of the lesion, and if nystagmus is present, the fast phase is away from the side of the lesion. Horizontal nystagmus may be peripheral or central. Vertical nystagmus is always associated with central nervous system disease. With otitis, although the head tilt may be severe, there should be no proprioceptive or mentation abnormalities. However, many rabbits become very agitated, and so may seem duller or quieter, or conversely more agitated than normal.
The anatomy of the rabbit ear canal is similar to other species. There is the pinna, and just cranial to the opening of the ear canal is a 'blind' pocket (called the pretragic incisure). There is a long vertical canal, and a short horizontal canal, and then the tympanum, which separates the external ear from the middle ear. The middle ear contains the ossicles, and the inner ear contains the semicircular canals and cochlea. The bulla lies at the base of the ear, and radiographically, the medial and lateral walls are very slightly thicker than the dorsal and ventral walls. The facial nerve runs near the bulla, with anatomic variation between individuals, so in some rabbits it may lie directly ventral to the bulla and in others it may be directly superficial to the bulla. Because of its anatomic location, in some rabbits with bulla osteitis, facial nerve contracture or paralysis may be present, and in any rabbit with asymmetric facial nerve examination, otitis and bulla disease should be considered.
Rabbits normally produce wax in the ear canals, which is brownish or slightly off-white and may serve a protective function. However, if the distal aspect of the canal cannot be visualized, it may be necessary to clean and remove this wax to facilitate more thorough otoscopic examination. (Note: ear mites have a crusty thick appearance, and when present can be easily diagnosed by obtaining a small swab sample and evaluating microscopically with mineral oil. Removal of these crusts and scales is not necessary; treat with ivermectin or selemectin and repeat in 2 weeks). If there is inflammation in the ear canal, or exudate which is white and creamy, perform a thorough otoscopic exam and evaluate the integrity of the tympanum. Obtain samples for cytology and culture, and evaluate cytologically for the presence of bacteria and/or yeast. If the tympanum is intact and the accumulation of exudate is mild, then any ear solution that does not contain steroids may be used to clean the ear canal. However, if the tympanum is ruptured, only warmed sterile saline should be used to clean the ear canal, as any fluid may have the potential to contact the brain.
Lop-eared rabbits are more prone to otitis. Common bacteria involved in otitis include Pasteurella multocida, Pseudomonas sp., Staphylococcus spp., and Streptococcus spp. However, many other bacteria may be present, so cultures should be obtained whenever possible. Yeast may also be present. Topical treatment should be initiated, using a product that does not contain steroid. In many patients, ophthalmic drops of an appropriate antibiotic can be used if an ear medication is not available without steroids. Standard yeast medications can be used. In many cases, systemic antimicrobials may also be necessary. Although steroids cannot be used, non-steroidal anti-inflammatory medications may be administered (including meloxicam, carprofen, ketoprofen, and topical NSAIDS).
For severe otitis media, deep ear lavage is beneficial to remove the debris. Because of the deep vertical canal, it is often impossible to reach the bottom of the ear canal with cotton swabs for cleaning. Deep ear lavage can be performed with a red rubber tube (3.5 to 8 French, use the largest size that will fit in the ear canal). Sedation or anesthesia may be required in painful or fractious rabbits. Using warmed sterile saline, and a syringe (20 cc for most rabbits), the canal is gently lavaged and suctioned, cleaning the debris and lavaging until the canal appears clear. If there is still debris which does not seem to b breaking up, then the procedure can be repeated several days later. Topical products designed to break down wax are available; again, choose only products without steroids.
If the infection is behind the tympanum, then a myringotomy can be performed. This is done endoscopically, to open the tympanum and lavage the middle ear. Again, sedation is required.
For severe otitis with head tilts, radiographs or CT scan should be performed to evaluate the bullae. Sedation is necessary. At least 4 views should be obtained; lateral, ventrodorsal, and right and left obliques. If possible, CT scan provides a greater degree of visualization and may detect more subtle changes or fluid. If bulla disease is present, bulla osteotomy (and total ear canal ablation, if indicated) can be considered. Although an aggressive surgery, it may ultimately alleviate long term pain as well as the need for repeated ear lavages.
Encephalitozoon cuniculi
Encephalitozoon cuniculi is an obligate intracellular protozoan organism that is commonly found in pet rabbits. There are 3 strains that have been identified: Type I (in rabbits), type II (in small rodents such as rats and mice), and type III (in dogs). This microsporidian parasite has been recognized since 1923 in laboratory rabbits. In the pet population, various studies have identified a seroprevalence range of 20-50% in tested rabbits with populations identified in the United States, Europe, and Australia. No sex or age prevalence is noted, and although dwarf rabbits have historically been over-represented, more recent studies contradict this finding. Serological studies suggest human exposure to microsporidial organisms may be a common occurrence, but without clinical significance in immunocompetent people.
Spores are shed in the urine of infected rabbits and are transmitted via ingestion or inhalation of urine-contaminated feed, or in utero. E. cuniculi spores can stay stable in environment for 4 weeks, but are inactivated by most routine disinfectants. In the acute phase of the infection (within 30 days of exposure), the organism replicates in the lung, liver, and kidney. In chronic infections (100 days post exposure), the brain and heart are additionally infected. Clinical signs are the result of inflammation and granuloma formation around the replicating organism at these sites. Asymptomatic infections are far more common than clinical disease in infected rabbits.
The most recognizable clinical symptoms are the vestibular signs including head tilt, rolling, circling, and nystagmus. Posterior paresis, ataxia, and seizures may also occur. Ocular lesions such as cataracts, phacoclastic uveitis, and hypopyon are usually unilateral and can affect the rabbit's ability to see out of the affected eye. Symptoms of renal disease may not be as easily recognized by owners, but can include urinary incontinence, urine scald, and polydipsia and polyuria. Weight loss from a protein-losing nephropathy may also occur. E. cuniculi infections can be limited to one organ system or can be multisystemic.
Serology to detect antibodies is often used to make a presumptive diagnosis of an E. cuniculi infection. It is important to remember that the health status of the patient must be taken in consideration when evaluating the serology results. A positive titer in a healthy animal only indicates exposure to the organism and is not prognostic for development of clinical signs. If a healthy rabbit is seronegative, it should be retested in 4 weeks in case the patient was recently infected and has not yet mounted an immune response. In a clinically ill rabbit, a very high or rising paired titers is suggestive, but this does not provide a definitive diagnosis that E. cuniculi is the causative agent. Once infected, the rabbit will remain seropositive for life, independent of the development of clinical signs. A negative titer in a clinically ill rabbit does, however, help rule out E. cuniculi as the cause of disease. Laboratory methods used to detect antibodies include indirect immunofluorescence, carbon immunoassay, ELISA, complement fixation, immunoperoxidase, and microagglutination. Polymerase chain reaction (PCR) can be used to detect E. cuniculi DNA in the kidney, brain, lens, urine, and cerebral spinal fluid. Although PCR is a sensitive and specific test, localized infections may yield negative results if a non-infected tissue is sampled. Additionally, the intermittent excretion of spores in the urine may also yield negative results. At this time, PCR testing for E. cuniculi is not commercially available. Histopathology of infected tissues demonstrates granulomatous inflammation and microscopic abscessation. The spores may or may not be present within the areas of inflammation. Other diagnostic tests recommended in the work-up in an E.cuniculi suspect include a CBC and biochemistry, urinalysis, and radiographs of the skull and/or spine (depending on the rabbit's clinical signs).
Treatment entails the administration of antiprotozoal medications such as fenbendazole (20 mg/kg PO q24h x 28 days), albendazole (30 mg/kg PO q24h x 30 days, then 15 mg/kg PO q 24 hr x 30 days) or oxibendazole (30 mg/kg PO q24h x 7-14 days). Though controversial, some clinicians advocate the limited use of a short-acting steroid, such as dexamethasone (0.1 mg/kg) to decrease any inflammation caused by the infection. Antibiotics are also often administered concurrently in case of secondary bacterial infections but are ineffective for E. cuniculi. Antibiotics commonly administered include enrofloxacin (10 mg/kg PO q12-24h x 10d), oxytetracycline (20 mg/kg SC q24h x 10d), or chloramphenicol (50 mg/kg SC q24h x 7d). Meclizine (2-12 mg/kg PO q24h PRN) can be administered to those rabbits experiencing severe head tilts or rolling. For those rabbits that are exhibiting true seizures, diazepam (1 mg/kg IM or 0.5-1.0 mg/kg IV) or midazolam (0.5-1.0 mg/kg IM) can be administered. If rabbits are anorexic, supportive care must be provided. Maintain hydration with subcutaneous fluids (100-150 ml/kg/day) and provide syringe feeding with Oxbow Critical Care until the rabbits are eating again on their own.
Prognosis can vary and rabbits can recover from a mild infection with no treatment at all. Head tilts may or may not resolve with treatment, and afflicted rabbits can learn to adjust to living with a head tilt. Rabbits that are exhibiting seizures or renal disease carry a worse prognosis of recovery. To prevent spreading the infection, seronegative rabbits should be kept isolated from seropositive rabbits and owners should always be advised to quarantine any new acquisitions until the rabbit's antibody status is determined.
In summary, otitis media is characterized by debris in the ear canal, a head tilt towards the affected side, and lack of other neurologic deficits. If present, nystagmus will have a fast phase away from the affected ear. Always perform a thorough otoscopic evaluation with cytology and cultures, and if there is a suspicion of bulla involvement, radiographs or CT scan should also be performed. Clean ears with a commercial steroid-free cleaning solution if the tympanum is intact, but only use sterile saline if the tympanum is ruptured or cannot be visualized. For severe cases, myringotomy or bulla osteotomy can be performed. Topical therapy should always be utilized, and systemic therapy should be instituted if there is inflammation of the ear canal or rupture of the tympanum. Treatment should be continued for 3 weeks and evaluated for the need for further treatment at that interval.
Deeb JB, Carpenter JW. Neurologic and Musculoskeletal Diseases. In Quesenberry KE, Carpenter JW, eds. Ferrets, Rabbits, and Rodents: Clincal Medicine and Surgery, 2nd ed. Philadelphia, Saunders, 2003, pp. 203-210.
Keeble EJ, Shaw DJ. Seroprevalence of antibiotics to Encephalitozoon cuniculi in domestic rabbits in the United Kingdom. Veterinary Record (2006) 158: 539-544.
Baneux PJ, Pognan F. In utero transmission of Enchephalitozoon cuniculi strain type I in rabbits. Laboratory Animals (2003) 37, 132-138.
Harcourt-Brown F. Radiographic signs of renal disease in rabbits. Veterinary Record (2007) 160:787-794.
Suter C, et al. Prevention and treatment of Encephalitozoon cuniculi infection in rabbits with fenbendazole. Vet Rec 2001; 148[15]:478-80
Lisa M. Felchle and Ron L. Sigler. Phacoemulsification for the management of Encephalitozoon Cuniculi -induced phacoclastic uveitis in a rabbit. Veterinary Ophthalmology (2002) 5, 3, 211–215
Antonella Tosoni A, et al. Disseminated Microsporidiosis Caused by Encephalitozoon cuniculi III (Dog Type) in an Italian AIDS Patient: a Retrospective Study Mod Pathol 2002;15(5):577–583
Mathis A et al. Zoonotic Potential of the Microsporidia. Clinical Microbiology Reviews (2005) 18: 423-445.
Popesko P, Rajtova V, Horak J. A Colour Atlas of Anatomy of Small Laboratory Animals. Volume 1. Saunders, 2002.