a 7-year - old spayed domestic longhair cat from perth , western australia , presented with left - sided head tilt , dysphonia , head shaking , inappetence and weight loss .
otitis media with extension into the external ear canal was suspected and investigated using video - otoscopy and computed tomography examination .
invasive disease with extension from the middle ear to the base of the skull , and intracranial extension into the caudal fossa and cranial cervical vertebral canal was detected .
cytology of external ear canal exudate showed capsulated budding yeasts and cryptococcus gattii vgii was cultured .
treatment with amphotericin b infusions and oral fluconazole was prescribed , with nutritional support via oesophagostomy tube .
this case report describes the successful medical treatment of otogenic meningoencephalomyelitis due to c gattii ( vgii ) infection in a cat .
cryptococcosis is a common systemic mycosis affecting cats worldwide and can affect cats of any age and sex .
the two most common species causing disease in animals are cryptococcus neoformans and cryptococcus gattii .
historically , cryptococcus was classified into five serotypes ( a , b , c , d and ad ) on the basis of antigenic differences in capsular polysaccharides . using a modern molecular typing scheme ,
cryptococcal strains are now divided into eight multilocus sequence types ( vni , vnii , vniii , vniv , vgi , vgii , vgiii , vgiv ) , which are likely to be cryptic species .
c gattii has been associated with tropical and subtropical climates , with an outbreak of disease affecting both humans and animals in the pacific northwest of the usa , emanating from an initial focus of infection on vancouver island , british columbia , canada . 

c gattii primarily infects immunocompetent hosts and the organism can cause disease in unusual host species ( eg , horses , ferrets , goats , dolphins ) .
vgii has a high environmental presence in perth , western australia , and areas of the northern territory , in contrast to eastern australia where vgi isolates predominate .
the genetic diversity of vgii environmental and clinical isolates obtained from the perth environs suggests there is a sexually recombining population structure in this geographical niche . while c gattii vgi is strongly associated with detritus in mature eucalyptus tree hollows , the ecological niche of vgii is largely unknown . in vancouver island , where an outbreak of vgiia was diagnosed in humans and animals , c gattii vgii colonises coniferous , evergreen and deciduous trees in the douglas fir tree bioclimatic zone , with transient isolation from soil , saltwater , freshwater and air .
infection most likely occurs subsequent to inhalation of airborne infectious propagules such as basidiospores or desiccated yeast cells with clinical signs of sneezing , stertor , nasal deformity and discharge reflecting nasal cavity infection .
it is common for the infection to spread , both locally to contiguous adjacent structures and haematogenously to other sites .
we present an unusual case of otogenic infection with intracranial extension attributable to c gattii vgiib in a cat for which signs resolved with aggressive medical therapy .
a 7-year - old spayed domestic longhair cat was presented to murdoch university veterinary hospital for evaluation of left head tilt , dysphonia , head shaking , inappetance and weight loss of 2 weeks duration .
initial investigations by the referring veterinarian identified an aural mass in the left horizontal ear canal , which had been removed .
sabouraud s dextrose agar culture of an ear swab had resulted in heavy growth of c gattii .
serum latex cryptococcal antigen agglutination test ( lcat ) was positive , with a titre of 1:256 .
the cat was treated with enrofloxacin ( 5 mg / kg po q24h [ baytril ; bayer animal health ] ) , itraconazole ( 10 mg / kg po q24h [ sporanox ; janssen pharmaceutica ] ) , meloxicam ( 0.05 mg / kg po q24h [ meloxicam ; troy laboratories australia ] ) and a topical compounded enrofloxacin / dexamethasone otic preparation .
the cat was thin ( body condition score [ bcs ] 3/9 ; weight 4.9 kg ) and had a left - sided head tilt .
the remainder of the clinical examination , including full ophthalmic and neurological examinations , was unremarkable .
the presence of a head tilt without ipsilateral postural reaction deficits was consistent with left peripheral vestibular disease .
hand - held otoscopic examination demonstrated a mass occluding the lumen of the left horizontal ear canal , and ceruminous discharge .
the cat was premedicated with buprenorphine ( 0.018 mg / kg i m [ temgesic ; symbion pharmacy services ] ) and acepromazine ( 0.04 mg / kg i m [ acp ; westralian holdings ] ) , anaesthetised with propofol and maintained with isoflurane in 100% oxygen .
a ct ( siemens emotion duo 2 slice ct scanner ; ge healthcare australia ) examination of the head was performed using soft tissue and bone spatial reconstruction algorithm and 1 mm slice thickness pre- and postintravenous contrast ( iohexol ; 10 ml [ 300 mmol / l ] iv ) ( figure 1 ) , followed by video - otoscopic examination .
( a ) the medial portion of the left external ear canal is filled with strongly and homogeneously contrast - enhancing soft tissue attenuating material ( 1 ) .
the left tympanic bulla is filled with mildly and homogeneously contrast - enhancing material ( 3 ) .
( b ) the material seen ventromedial to the tympanic bulla continues caudally and forms a 1.6 cm ( width )  1.3 cm ( height )  2.5 cm ( length ) soft tissue structure , poorly enhancing centrally but strongly enhancing peripherally ( 1 ) .
this mass ( * ) distorts local tissue architecture such that the nasopharyngeal lumen is narrowed > 50% , and the hyoid bones are displaced laterally .
additionally , at this level , there is a rim of contrast enhancement seen in the ventral aspect of the left temporal lobe of the cerebrum ( 2 ) .
( c ) at the level of the caudal aspect of the left tympanic bulla , the soft tissue lesion can still be seen ventromedial to the bulla ( 1 ) .
additionally , there is a rim of contrast enhancement outlining a hypoattenuating area in the left lateral cerebellum ( 2 ) .
there is poorly contrast - enhancing soft tissue attenuating material in the caudal fossa that is displacing the brainstem dorsally and to the right ( 3 ) . additionally , there is strong meningeal contrast enhancement in this region .
( d ) the poorly contrast - enhancing material in the cranial cavity can be followed further caudally , to the level of the atlas .
this image , at the level of the foramen magnum , demonstrates abnormal tissue ( arrow ) displacing and compressing the cervical spinal cord ( * ) dorsally and to the right .
( e ) bone window computed tomography image at the most caudal aspect of the bulla .
note the discontinuity of the temporal bone ( black arrows ) , indicative of bony lysis ct showed moderate contrast enhancement of the left ear canal lining .
the medial portion of the left external ear canal and left tympanic bulla were filled with homogenous , contrast - enhancing soft tissue attenuating material ( figure 1a ) .
ventromedial and rostral to the tympanic bulla , a region ( 1.6 cm width  1.3 cm height  2.5 cm length ) of poorly contrast - enhancing tissue , outlined by a rim of strong contrast enhancement ( figure 1b ) causing a mass effect , was seen , which compressed the nasopharyngeal lumen by > 50% and displaced the hyoid bones laterally ( figure 1b ) .
ventromedial and caudal to the bulla , a similarly enhancing region was seen ( 0.6 cm height  0.3 cm width  0.6 cm length ) . in the caudal left bulla , there was bony lysis of the temporal bone ( figure 1e ) .
lateral to the oval foramen and dorsal to the larger parapharyngeal lesion , an intracranial rim of contrast enhancement was seen in the ventral aspect of the left temporal lobe .
adjacent to the lytic region of the temporal bone , contrast enhancement outlining a hypoattenuating area with broad dural base was seen ( figure 1c ) . poorly enhancing material extended caudally along the left ventral portion of the brainstem to mid first cervical vertebra , displacing and compressing the brainstem and cranial spinal cord , accompanied by strong meningeal contrast enhancement ( figure 1d ) .
video otoscopy ( medrx video otoscope ) identified a large pink fleshy mass obscuring the lumen of the horizontal ear canal .
the mass traversed the tympanic membrane , and was contiguous the tympanic bulla ( figure 2 ) , in agreement with ct findings .
video - otoscopic photograph of the left tympanic membrane , which appears to have been breached by abnormal inflammatory tissue ( arrows ) , which extends into the tympanic bulla impression smears of the mass revealed large numbers of round yeast , surrounded by a prominent clear halo and narrow - necked budding consistent with cryptococcal infection .
a heavy pure growth of a cryptococcus species resulted , which was identified as c gattii by conventional phenotypic mycology testing .
further analysis by sequencing of the ribosomal internal transcribed spacer region identified c gattii vgii by comparing the sequence with published signature sequences ; however , the isolate was not available for further molecular typing .
the isolate was susceptible to fluconazole , itraconazole , posaconazole , flucytosine and amphotericin b , but resistant to caspofungin .
the minimum inhibitory concentration ( mic ) for fluconazole was 8 mg / l ( table 1 ) .
antifungal susceptibility data for the cryptococcus gattii vgii isolate cultured from the cat s = susceptible ; r = resistant ; mic = minimum inhibitory concentration antifungal therapy was commenced with fluconazole ( 10 mg / kg po q12h [ symbion pharmacy services ] ) and amphotericin deoxycholate ( 0.5 mg / kg ; subcutaneous infusion in 350 ml 0.45% nacl and 2.5% dextrose three times weekly ) .
four weeks after treatment commenced , the cat was brighter , with complete resolution of the head tilt , although inappetence persisted .
, the cat had received a cumulative amphotericin b dose of 12.5 mg / kg , and was starting to eat and gain weight . owing to finances ,
the frequency of amphotericin b infusion was reduced to twice weekly ( dose 0.7 mg / kg / infusion ) .
the frequency of amphotericin b infusion was reduced to once weekly ( 0.7 mg / kg / infusion ) .
four months after diagnosis , lcat was 1:256 and the plasma concentration of fluconazole was 45 mg / l .
seven months after diagnosis , the lcat was 1:64 and was 1:32 a further 3 months later , with a corresponding plasma concentration of fluconazole of 47 mg / l .
after 12 months , the weekly amphotericin b infusions ( 0.7 mg / kg ) were discontinued and the cat continued to be clinically well , receiving only fluconazole ( 50 mg q12h ) . at the time of writing , 21 months after starting therapy , the lcat was 1:8 and the cat continued to be clinically well .
otitis media due to c neoformans var grubii infection was managed by a total ear canal ablation and lateral bulla osteotomy , followed by oral itraconazole . in the third cat ventral bulla osteotomy and twice weekly amphotericin b subcutaneous infusions , with oral flucytosine and fluconazole , were used . in these latter two cats ,
diagnosis was made on cytological and histological evaluation of material removed via bulla osteotomy , culture and serum antigen testing .
the cat presented initially with unilateral peripheral vestibular disease . as a mass in the left external ear canal
was detected during preliminary examination , an aural polyp arising from the middle ear was initially suspected .
presence of additional signs , including dysphonia , inappetence and weight loss , may have suggested a more sinister underlying aetiology .
cytology from the external ear canal resulted in a prompt diagnosis of cryptococcosis ; however , failure to improve clinically to azole monotherapy prompted referral .
video otoscopy and ct of the head demonstrated extensive and invasive disease of the ear , skull , cervical spinal cord and ipsilateral intracranial dural space .
inhalation of air - borne basidiospores or desiccated yeast cells into the nasal cavity is considered the primary route of infection in cats .
colonisation of the caudal nasal cavity , with subsequent epithelial invasion , possibly in the vicinity of the nasopharynx , may have been the primary route of infection , with extension via the auditory tube to the middle ear .
possible pathways from the inner ear into the brainstem include erosion through the medial aspect of the petrous temporal bone ( although this was not apparent in the ct scans ) , along the nerves and vessels of the internal acoustic meatus , or via haematogenous spread .
inoculation of cryptococcal organisms directly into the external ear canal , with subsequent spread to the middle ear by penetration of the tympanic membrane is considered unlikely and usually results in only superficial lesions .
a grass seed heavily contaminated with cryptococcal cells may provide an explanation for how this might have occurred , although these are less commonly found in the ear canal of cats than dogs .
this case is quite distinct from a recent feline case of bilateral cryptococcal otitis interna , which was thought to have arisen haematogenously as there was no evidence of rhinosinusitis disease or otitis media , and a small cryptococcal lesion was also present in the thalamus ; this patient was infected with c neoformans var grubii .
the pathogenesis of cryptococcus in this cat is unusual and supports the contention by sykes and malik that vgii and vgiii infections are more invasive than c gattii vgi and c neoformans var grubii infections .
all clinical signs resolved after aggressive medical therapy and initial de - bulking within the ear canal . while recent papers concerning c gattii vgi infections of the nasal cavity and contiguous tissues in koalas have emphasised the need for surgical intervention and/or intralesional therapy because antifungal agents may not penetrate well into poorly perfused tissues , the requirement for this probably should be made on a case - by - case basis .
c gattii vgii can be divided into vgiia , vgiib and vgiic strains , with vgiia being the major genotype in the vancouver island outbreak .
determining the specific biotype is critical because c gattii vgii and vgiii isolates tend to demonstrate heteroresistance to fluconazole .
the epidemiological cut - off values for fluconazole in vgii and vgiii infections are therefore higher than for vgi and c neoformans var grubii isolates . in this instance
the causal vgii isolate was susceptible to fluconazole in vitro , with a mic of 8 mg / l . given the pharmacokinetics of fluconazole in the cat , a dose of 10 mg / kg po q12h should produce peak blood concentrations of fluconazole at steady state in the order of 2080 mg / l . in eastern australia , about 20% of cryptococcosis in cats and dogs is caused by c gattii ( predominantly vgi ) . in western australia , vgiib ( mating type  ) is the predominant species of c gattii , although vgi and vgii ( mating type a ) also occur .
studies on the c gattii vgiia isolates from the vancouver island outbreak and vgiib isolates from australia have demonstrated that such strains are highly virulent in experimental infections of mice and rats .
although central nervous system ( cns ) involvement is an important negative prognostic indicator in feline cryptococcosis , this cat improved markedly with combination therapy using amphotericin b and fluconazole .
cross - sectional imaging was not often undertaken when cases of cryptococcosis were first recorded in the veterinary literature . in this case ,
clinical findings and plain radiographs would not have provided indication of the extensiveness of the disease , and the success of medical therapy in this cat testifies that good outcomes may occur despite extensive invasive disease .
treatment for cns cryptococcosis is prolonged and should be continued until the lcat titre reaches zero , which may take 12 years . in recovered cats ,
the titre can be monitored every 36 months to allow early detection of recurrences , which is more common than re - infection with a new strain or antifungal resistance .
this case report describes the successful medical treatment of otogenic meningoencephalomyelitis due to c gattii ( vgii ) infection in a cat .
 case summarya 7-year - old spayed domestic longhair cat from perth , western australia , presented with left - sided head tilt , dysphonia , head shaking , inappetence and weight loss . 
 a polypoid lesion had previously been removed from the external ear canal . 
 otitis media with extension into the external ear canal was suspected and investigated using video - otoscopy and computed tomography examination . 
 invasive disease with extension from the middle ear to the base of the skull , and intracranial extension into the caudal fossa and cranial cervical vertebral canal was detected . 
 cytology of external ear canal exudate showed capsulated budding yeasts and cryptococcus gattii vgii was cultured . 
 treatment with amphotericin b infusions and oral fluconazole was prescribed , with nutritional support via oesophagostomy tube . 
 the cat clinically recovered 12 months after treatment commenced.relevance and novel informationthis case report describes the successful medical treatment of otogenic meningoencephalomyelitis due to c gattii ( vgii ) infection in a cat . 