A 4-year-old female spayed domestic shorthair cat weighing 6.9 kg was presented with a 2-week history of intermittent bilateral exophthalmos, facial swelling and serous ocular discharge. Food prehension, the ability to open the mouth and pre-referral intraoral radiographs were unremarkable. Owing to a lack of visible clinical improvement following clindamycin (Zodon; Ceva) treatment, amoxicillin–clavulanic acid (Noroclav; Norbrook) and meloxicam (Metacam; Boehringer Ingelheim), the cat was referred to the neurology and neurosurgery service at the Animal Health Trust.\nAt presentation, generalised facial swelling, extending to the neck and cheeks, mild exophthalmos, third eyelid protrusion, chemosis and bulbar conjunctival hyperaemia were detected bilaterally (). The left eye was more severely affected than the right. Aqueous flare was absent and intraocular pressure, menace response and pupillary light and dazzle reflexes were unremarkable. Fluorescein staining was negative bilaterally and the Jones test was positive in the right eye only. Performing complete physical and neurological examinations was not possible given the uncooperative nature of the cat; however, the remainder of the physical examination under general anaesthesia was unremarkable. A disease affecting the retrobulbar area or the masticatory muscles, including masticatory myositis (MM), was suspected.\nHaematology and serum biochemistry revealed mild eosinophilia (3.38 × 109/l; reference interval [RI] 0.10–2.00) and a markedly elevated creatine kinase (CK) activity (5959 IU/l; RI 70–190). Serological titres against Toxoplasma gondii were consistent with previous exposure.\nMRI of the head was conducted with a 1.5 T scanner (Signa EchoSpeed; GE Healthcare). Transverse, dorsal and sagittal T2-weighted (T2W) (repetition time [TR] 3975–6221 ms/echo time [TE] 84–87 ms; field of view 140 mm, matrix 512 × 512) sequences, transverse precontrast T1-weighted (T1W) (TR 521 ms/TE 6.6 ms) images, and transverse and dorsal postcontrast T1W sequences – after the administration of an intravenous gadolinium-based agent (Gadovist; Bayer) – were obtained. Additionally, transverse short tau inversion recovery (STIR) (TR 8344 ms/TE 39 ms/TI 150 ms) and transverse postcontrast T1W images with fat saturation (TR 732 ms/TE 6.6 ms) were acquired. Slice thickness was 3 mm.\nThe temporal, masseter and medial pterygoid muscles were diffusely thickened bilaterally and showed multifocal-to-coalescing areas of marked hyperintensity on T2W and STIR images relative to normal muscle (). There were subtle hyper- and hypointensities on T1W images, producing an ill-defined striated appearance. The affected muscles showed strong and heterogenous contrast enhancement, with multiple embedded, non-contrast-enhancing areas (consistent with fluid or necrosis) within the abnormal muscles (,). The digastricus, extraocular and cervical muscles appeared to be unaffected. Significant mandibular and medial retropharyngeal lymphadenopathy was detected. The MRI was suggestive of severe infectious or immune-mediated MM.\nAs a feline-specific assay has not been established, a canine ELISA was used to detect serological titres against type IIM muscle fibre proteins and was positive at a dilution of 1:4000 (RI <1:100 in dogs). Cytological analysis of ultrasound-guided fine-needle aspirates of the left temporal and masseter muscles, including the suspected necrotic regions on MRI, revealed eosinophilic and macrophagic inflammation. Bacterial and fungal cultures were negative. Lack of evidence supporting active infection coupled with positive serological titres against type IIM muscle fibres supported the diagnosis of immune-mediated MM.\nElectromyography (EMG) was performed using digital electrodiagnostic equipment (Medelec Synergy; Oxford Instruments). The temporal, masseter, epaxial and pelvic and thoracic limb appendicular muscles were assessed. Normal insertional activity was recorded and no electrical activity abnormalities were identified.\nOpen muscle biopsy samples were obtained from the left temporal muscle. Both fresh refrigerated and formalin fixed samples were sent to the Comparative Neuromuscular Laboratory at the University of California, San Diego, by a courier service, for complete histopathological examination. The biopsies showed a moderate variability in type IIM myofibre size with scattered atrophic fibres having a round shape. Fibre type grouping was not observed and intramuscular nerve branches appeared normal. Multifocal areas of mononuclear cell infiltrations (lymphocytes and acid phosphatase/esterase reactive macrophages) had an endo- and perimysial distribution. Peroxidase reactive eosinophils were not identified. Scattered necrotic fibres were undergoing phagocytosis. Moderate perimysial fibrosis was observed. No fibre loss, organisms or cytoarchitectural abnormalities were identified. A multifocal inflammatory myopathy (myositis) with mild perimysial fibrosis and no obvious myofibre loss was diagnosed ().\nConsequently, the diagnosis of immune-mediated MM was established. The cat was started on an immunosuppressive dose of prednisolone (30 mg; 4.4 mg/kg q24h [Prednidale; Dechra]). The dose was decreased every 6 weeks with the aim of discontinuing administration 36 weeks after the initiation of treatment. Repeating the measurement of serum CK activity and serological titres for type IIM myofibres prior to decreasing the dose of prednisolone was recommended on each occasion. However, owing to the cat’s non-compliant behaviour, this was not achieved. Frequent email and telephone communications were maintained with the cat’s owner and photographs of the cat’s face were regularly checked.\nThree months after starting treatment (prior to decreasing the prednisolone dose from 2 mg/kg q24h to 1 mg/kg q24h), the serum CK activity and type IIM myofibre titres were 387 IU/l and negative at <1:100, respectively. Ten months after initial presentation, while receiving prednisolone at 1.5 mg (0.2 mg/kg) q48h for 6 weeks, the cat showed mild lethargy and an episode of unprovoked aggression to a family member. No changes in facial expression were noticed. At this point, the serum CK activity was within the RI and type IIM myofibre titres were positive at 1:500. Repeating muscle biopsies was recommended by the authors but declined by the owner. The prednisolone dose was therefore increased to 15 mg (2.1 mg/kg) q24h. Type IIM myofibre titres returned to within the RI (<1:100) and the prednisolone dose was halved after 2 months. Titres remained negative 6 weeks later inciting a further decrease in prednisolone dose to 5 mg (0.7 mg/kg) q24h. Following unremarkable blood tests 2 months after the prednisolone dose reduction, a further decrease in dose to 2.5 mg (0.35 mg/kg) q24h was implemented. Five months later, despite the cat appearing clinically normal, type IIM myofibre titres became positive at 1:500. Until this time, no significant side effects of prednisolone had been observed. The prednisolone dose was increased to 5 mg (0.7 mg/kg) q24h and ciclosporin (Atopica oral solution; Elanco) was started at 4 mg/kg q12h and continued to date. Three months later, negative type IIM myofibre titre tests were achieved. Ensuing polyphagia and weight loss prompted the performance of blood analyses, and the cat was diagnosed with diabetes mellitus. Appropriate treatment was started by the primary care veterinary surgeon; the prednisolone dose was halved (2.5 mg; 0.35 mg/kg q24h) and gradually discontinued. Immunosuppressive treatment was continued with ciclosporin alone (for 60 days at the time of writing). No reoccurrence of neurological clinical signs has been reported to date, with a follow-up of 27 months after initial diagnosis.
An 8-year-old tortoiseshell spayed female domestic shorthair cat was referred for anorexia, weight loss and progressive trismus of at least 1 month duration. A history of chronic rhinitis since the age of 4 months was reported. A PCR test for calicivirus was negative. Previous antibiotic therapies (doxycyline 10 mg/kg PO q24h for 10 days; benzylpenicillin procaine 7 mg/kg [dihydrostreptomycin 10 mg/kg long-acting formulation] IM; and clindamycin hydrochloride 11 mg/kg PO q24h for 10 days) did not result in any clinical improvement. The cat was exclusively fed veterinary dry food and no history of trauma was reported.\nUpon presentation, the cat had generalised weakness, bilateral purulent nasal discharge, with concurrent reduced nasal airflow, right epiphora with chemosis and third eyelid protrusion, and concurrent mild bilateral mandibular lymph node enlargement. Body condition score was 3/9 (weight 2.9 kg [6.4 lb]). Neurological examination revealed decreased bilateral palpebral reflexes on the ophthalmic branch territories of the trigeminal nerves, and an absence of pupillary light reflexes. Vision testing revealed complete visual deficits, previously unnoticed by the owners, absent menace response in both eyes, and the patient bumping into objects. Spinal reflexes were normal and no gait abnormality was present. Oral examination showed painful mouth opening with a restricted vertical mandibular range of motion (vmROM), and an inability to close the mouth (). The rest of the physical examination was within normal limits.\nSerum biochemistry and electrolytes were unremarkable. Serological screening for infectious agents (Toxoplasma species, Ehrlichia species, Cryptococcus species, Anaplasma species) was negative. A complete blood count and blood smear examination revealed a mild microcytic non-regenerative normochromic anaemia with concurrent moderate neutrophilia and monocytosis. Antinuclear antibody testing was negative, and creatine kinase activity, activated partial thromboplastin time, activated clotting time, thrombin clotting times and D-dimers were within the normal limits. The restriction of vmROM persisted under general anaesthesia (22 mm). Intra-oral examination and dental charting revealed oropharyngeal swelling, with haematomas involving the retromolar areas, ulceration of the dorsal aspect of the tongue and mild generalised periodontitis.\nIn order to explore the cause of reduced mouth opening, CT of the head was performed. Selected reconstructed images are provided (). CT images showed bilateral, asymmetrical, non-enhancing (49 Hounsfield units in the pre- and post-contrast images), ill-defined hypodense areas within the masticatory muscles, mostly the temporalis and masseter muscles. Irregular periosteal reaction was noted on the ramus of the mandible and on the parietal and temporal bones bilaterally. Some new bone foci extended into the temporalis and medial pterygoid muscles away from the bone surfaces, indicating an ectopic mineralisation disorder. CT findings suggested bilateral chronic masticatory myositis.\nSix ultrasound-guided needle-core biopsies from the right and left masticatory muscles were collected and submitted to two different laboratories for comparative anatomopathological analysis. Biopsied material was submitted fresh and fixed in 10% neutral buffered formalin and decalcified as required. Fresh biopsies were isopentane pre-cooled in liquid nitrogen for cryohistology. Cryosections were stained with haematoxylin and eosin, Engel’s modified Gömöri trichrome stain, oil red O and periodic acid–Schiff reaction. Fixed biopsies were embedded in paraffin, sectioned at 3–5 µm thickness, mounted on glass slides and stained with haematoxylin and eosin before light microscopy evaluation. The samples showed extensive replacement of the myofibers with a dense vascularised mesenchymal tissue exhibiting progressive ossification. The mesenchymal tissue was composed of peripheral fascicles of activated fibroblasts and intermediate osteoblasts depositing woven bone and gradually forming trabeculae of lamellar bone (). Rare atypia and mitoses were present in the fibroblastic population. Residual muscle fibres embedded in the lesions were atrophic and degenerated. Some samples revealed striated muscle containing occasional inflammatory infiltrates. No infectious agent was observed within the samples. A FOP-like disease was considered the most likely diagnosis by both laboratories.\nSupportive treatment during hospitalisation consisted of fluid therapy (3 ml/kg/h), nutrition through an oesophagostomy tube, antibiotic therapy (clindamycin hydrochloride 11 mg/kg PO q24h for 7 days, then doxycycline 10 mg/kg PO q24h), pain management (buprenorphine 20 µg/kg IV q6h), a muscle relaxant (dantrolene-sulfate 1 mg/kg PO q8h) and immunosuppressive doses of methylprednisolone (3.3 mg/kg PO q24h) in case of an immune-mediated process. The latter was subsequently replaced with robenacoxib (1 mg/kg PO q24h) 4 weeks after initial presentation.\nDespite weight stabilisation, and improved willingness to move, allowing transient home care, the cat failed to recover the ability to eat spontaneously. A full-body CT scan was eventually performed 4 weeks after initial presentation and excluded additional areas of soft tissue calcification, pulmonary lesions and lymph node enlargement. Five weeks after initial presentation there had been a rapid decrease of vmROM leading to a total inability to open and close the mouth (13 mm open bite). A persistent bilateral purulent nasal discharge with almost total blockage of the nares led to the decision to perform a tracheostomy and nasal cavity lavage under general anaesthesia. During induction of anaesthesia, an emergency endotracheal intubation by tracheotomy, followed by cardiac resuscitation, had to be carried out. Because of the worsening prognosis, the owners elected humane euthanasia and rejected post-mortem investigations.\nTwo remaining samples of fresh biopsied material, kept at –80°C, were ultimately sent in dry-ice medium to a specialised laboratory for molecular analysis. Genomic DNA was extracted from the muscle samples, using sodium dodecyl sulfate/proteinase K lysis followed by purification on silica columns. The primers were synthesised at a 25 nmol scale, desalted and designed on the reference sequence of Genbank NC_018730, with the use of a software. After PCR amplification and product purification Sanger sequencing was performed for the whole nine coding exons of Felis catus ACVR1 (total linear DNA length 222,790,142 bp), located on the C1 chromosome, and purified. DNA sequencing products were analysed on a 96 capillary DNA analyser. Two deletions were highlighted in the exon 8 and exon 9 PCR products, and were further amplified and sequenced. Both of them were characterised in intron 8, upstream of the last coding exon 9 of ACVR1. Four bases (TTGA) were deleted around –123 bases of the exon 9 start (position 139,512 of the total gene sequence), and five bases (CCCAT) were deleted around –225 bases upstream of the exon 9 start (position 139,410 of the total gene sequence).