When veterinary staff think of head tilts in exotic pets, their minds will often jump to rabbit patients and Encephalitozoon cuniculi. However, head tilts are not exclusively a condition of rabbits and are not exclusively a result of E. cuniculi, even in rabbits.
This article, therefore, discusses the most common presentations of head tilts in exotic small mammals and the management of the most common differentials for these cases. As rabbits are the most common exotic mammal species to present with a head tilt, however, the majority of this article will focus on the diagnosis and management of head tilts in this species.
Head tilts in rabbits – causes, diagnosis and management
There are three common causes of head tilt in rabbits that cause both acute and chronic presentations.
Encephalitozoon cuniculi infection
The most widely known is E. cuniculi, an obligate intracellular microsporidian fungi which is often thought to be the main cause of head tilts in rabbits (Figure 1). However, caution should be taken before assuming all rabbits with head tilts are affected with E. cuniculi without first confirming a diagnosis.
Transmission and pathophysiology
E. cuniculi is spread vertically in utero (Baneux and Pognan, 2003) or horizontally via inhalation or the ingestion of spores from infected urine (Künzel and Fisher, 2018). E. cuniculi spores remain highly infective in the environment and can remain viable for up to six weeks at 22°C (Künzel and Fisher, 2018).
A UK cohort study showed a seroprevalence of 52 percent in healthy rabbits sampled for E. cuniculi (Keeble and Shaw, 2006), so veterinarians should assume that at least half of the rabbits presenting with no clinical signs have been exposed. However, exposure does not mean clinical disease, which is an important distinction to make when testing rabbits for this organism.
A UK cohort study showed a seroprevalence of 52 percent in healthy rabbits sampled for E. cuniculi, so veterinarians should assume that at least half of the rabbits presenting with no clinical signs have been exposed
Once infected, the fungi affect the kidneys, liver and lungs, then eventually the brain (Künzel and Fisher, 2018). Rabbits can begin to shed infective spores from one month post-infection, with large volumes passed two months post-infection and the shedding of spores terminating at three months post-infection (Graham et al., 2022).
Ocular manifestations of E. cuniculi only occur if a rabbit is infected in utero. The proposed pathogenesis is that the lens tissue is infected during early lens formation, before the development of a protective capsule (Ozkan et al., 2019). As the rabbit ages after birth, microsporidia cause the rupture of the cells in the lens, resulting in a phacoclastic uveitis and pyogranulomatous inflammation that presents as the “acute onset cataract” formation often reported (Felchle and Sigler, 2002).
Clinical signs and diagnosis
Head tilts resulting from E. cuniculi infection occur due to vestibular disease, with clinical signs ranging from a mild to severe head tilt (Figure 2A), rolling (Figure 2B), nystagmus, ataxia, circling and seizures (Graham et al., 2022). Diagnosis is essential, as blanket treating these cases with fenbendazole without proof of infection risks ignoring other possible causes and has the potential to disrupt the gut microbiome by killing beneficial nematodes and possibly suppress the bone marrow.
Serology testing for immunoglobulin G (IgG) and immunoglobulin M (IgM) is possible in several laboratories throughout the United Kingdom. Elevations in IgM titres indicate a recent or reactivated infection, as IgM titres usually elevate between days 0 and 35 and then fall between weeks 8 and 15 (Latney et al., 2014). IgG titres indicate the patient has been exposed to E. cuniculi and present in three ways (Baney et al., 2021):
- A short response is defined by a decrease in IgG titres 45 to 63 days after the initial infection
- A long response is defined by IgG titres that continue to elevate beyond 63 days post-infection
- An episodic response is defined by repeated seroconversion, where IgG levels fluctuate
Urine polymerase chain reaction (PCR) testing is difficult, as the shedding of infective spores in urine is intermittent. However, PCR on lenses that have undergone phacoemulsification has been shown to be sensitive and specific (Latney et al., 2014).
Treatment and management
Treatment of E. cuniculi with fenbendazole only prevents replication of the organism; it does not completely remove the infection (Harcourt-Brown and Holloway, 2003). Long treatment courses of 30 to 60 days have been recommended (Graham et al., 2022). In cases with severe symptoms, supportive adjunct treatments should also be considered. Prochlorperazine can be administered to help with symptoms of vestibulitis and nausea. Non-steroidal anti-inflammatories (NSAIDs) should be considered if renal parameters are within normal limits on blood biochemistry.
Some rabbits infected with E. cuniculi will require intensive nursing care from the offset; this includes using rolled-up towels and soft bedding (Figure 3), hygiene care and offering food and water. Many patients are ravenous and will eat willingly without the need for syringe feeding. In the initial stages, some rabbits may benefit from anxiolytic therapy, such as midazolam, especially if the patient is prone to rolling with stress.
Toxoplasma gondii infection
While much less common than E. cuniculi, Toxoplasma gondii should be considered when working up a rabbit for causes of head tilt.
Infections with T. gondii can present with similar clinical signs of head tilt, vestibular disease or seizures. It should be considered in rabbits that have contact with cats or have access to a garden that can also be accessed by cats. A recent study in Finland showed T. gondii had a seroprevalence of 3.9 percent compared to a seroprevalence of 29.2 percent for E. cuniculi in a population of healthy pet rabbits (Mäkitaipale et al., 2022). Toxoplasma serology can be run in conjunction with E. cuniculi serology.
Otitis media
Another common cause of head tilts in rabbits is otitis media. This is especially prevalent in lop-eared rabbits. These rabbits are predisposed to developing otitis due to the point of flexion at the tragus, which results in an anatomical stenosis of the ear canal (Mancinelli and Lennox, 2017). A recent study indicated the most commonly cultured organisms from the middle ear of rabbits with otitis media included Pasteurella multocida, Bordetella bronchiseptica and Staphylococcus aureus (Monge et al., 2023).
Clinical signs and diagnosis
If otitis media advances, facial nerve paralysis and damage to the vestibular apparatus can occur. In severe cases where the vestibular apparatus is affected, rabbits can present with acute nystagmus, torticollis and ataxia. This can also present acutely when owners have not observed the subtle clinical signs, such as facial nerve paralysis or swelling at the ear base indicating a diverticulum – a common occurrence in these cases.
Otoscopic examination can give an indication of what is occurring in the external ear canal; however, a definitive diagnosis requires radiographs or computed tomography (CT). Skull radiographs can show evidence of increased radiopacity over the bullae, as well as sclerosis, periosteal proliferation or even lysis of the bone surrounding the affected bulla (Mancinelli and Lennox, 2017). CT is superior in diagnosing otitis externa, with the common findings including soft tissue attenuating material in the affected bulla or bullae and tympanic bulla lysis (de Matos et al., 2015) (Figure 4). A grading system to establish the extent of otitis media has been proposed by Richardson et al. (2019), which can aid in choosing a treatment modality.
Treatment and management
Medical management for otitis media is often unsuccessful, as topical antibiosis is unlikely to reach the area of infection and systemic antibiosis can have reduced effectiveness, as the infection sits within the bony surrounds of the bulla (Chow, 2011). However, analgesia must be provided in all cases diagnosed with otitis media, as it can be an incredibly painful condition.
Surgical options include a lateral wall resection and bulla osteotomy or a total ear canal ablation and bulla osteotomy. In some cases, the head tilt can fully resolve following surgery; however, no improvement or even a worsening of the condition has also been reported (Monge et al., 2023).
Head tilts in other exotic small mammals
While not as common in other small mammals, a head tilt is a not infrequent presentation in small rodents such as guinea pigs and rats. Head tilts in these smaller mammals are often the result of otitis media (Figure 5). However, other possible causes include trauma (Figure 6), toxicity or a central nervous system lesion. In rats, pituitary tumours are a common underlying cause of head tilts (Vannevel, 2006) (Figure 7).
There will often be other clinical signs associated with the head tilt, including ataxia, circling and nystagmus, and sometimes patients will be hyporexic or anorexic. Evidence of purulent discharge from the dependent ear pinna may help to narrow down a diagnosis of otitis, and clues as to the underlying cause may be present in the history.
Treatment and management
In cases of otitis in smaller mammals, a long course (three to six weeks) of antibiosis based on culture is often successful in alleviating the infection. Advanced imaging such as CT can help definitively diagnose otitis media or pituitary adenomas in rats; however, magnetic resonance imaging (MRI) may be required for central nervous system lesions. With supportive care, the prognosis for otitis media in small mammals is good.
Cabergoline has been used to medically manage and shrink a pituitary adenoma in a domestic rat (Mayer et al., 2011). It is currently the mainstay of treatment for this condition in rats, as surgical removal is not possible.
Conclusion
Head tilts are common in rabbits, but it should not be assumed that all are caused by E. cuniculi. While it remains one of the top differentials to consider in cases of head tilts in rabbits, otitis media should be carefully considered, especially in lop-eared rabbits. Similarly, in small companion mammals otitis media is a common cause of head tilts and should be investigated. Management of head tilts should depend on the species affected and the underlying cause but should always include analgesia and anti-nausea medications. Anxiolytics and prochlorperazine should be considered as part of the treatment regime.
