A 1-year-old male neutered mixed breed cat (4.6 kg) was presented for difficulty prehending hard food. The cat was housed strictly indoors. About 2 months prior to presentation, the owner noticed the cat was not fully opening its mouth when yawning but had been able to eat slowly, managing soft food and pieces of hard food. No other behavioral or clinical signs of disease were reported. On physical examination the cat was very bright, alert, appropriate and clinically well hydrated with a body condition score of 6/9. Owing to the long haircoat palpation was necessary to appreciate the severe bilaterally symmetrical atrophy of the masticatory musculature (). Ocular retropulsion and palpation of the mandibular lymph nodes were normal.\nAn intraoral examination was impossible owing to the decreased vertical mandibular range of motion (vmROM) of 11–12 mm as measured with a metric ruler between the upper and lower incisor tips (). Visible teeth were age appropriate and normal in appearance. Occlusion was symmetrical. Limited vmROM was smooth and without discernible crepitus, but had a firm endpoint at 12 mm. The remainder of the physical and neurological examinations was unremarkable. Owing to financial constraints and anesthetic risks associated with the restricted vmROM, CT to rule out osseous abnormalities and biopsy of a masticatory muscle were declined. Blood tests and skull radiography were approved.\nComplete blood count (CBC) values were unremarkable. Serum biochemistry values, including creatine kinase activity, were within normal limits, except for an elevation of alanine transferase (214 U/l; reference interval [RI] 10–100 U/l) and aspartate aminotransferase (176 U/l; RI 10–100 U/l) activities. Dorsoventral skull radiography showed no bony abnormalities associated with the temporomandibular joints or elsewhere in the skull. Since a feline-specific assay has not yet been established for the detection of antibodies against masticatory muscle type 2M fiber proteins, an established canine ELISA system was used to detect cross-reacting antibodies against canine type 2M fiber antigens. The serum 2M antibody titer was positive at a dilution of 1:1000 (RI <1:100 in dogs, and also <1:100 using serum from five archived normal cats). Circulating antibodies against type 2M fibers are diagnostic of MM in dogs.\nMethylprednisolone (Depo-Medrol; Zoetis) was administered intramuscularly (24 mg; 5.2 mg/kg). Forced jaw opening to improve vmROM was not performed owing to the risk of iatrogenic osseous fracture or soft tissue damage. Two weeks after the initial treatment, further examination revealed no change in the extent or character of vmROM. Appetite and activity remained good. Repeat CBC and serum biochemistry values were unremarkable. Oral prednisolone (Lloyd [5 mg; 1 mg/kg q12h]) was prescribed. One month later, in a follow-up telephone conversation with the owner, it was determined the oral prednisolone prescription had not been filled. The oral prednisolone prescription was subsequently filled and administered crushed in soft food. The cat was again evaluated almost 2 months after the initial presentation. Body weight was slightly increased (4.7 kg). The vmROM, as determined with a millimeter ruler in the relaxed conscious cat, remained restricted at 11–12 mm. Severe bilaterally symmetrical masticatory muscle atrophy persisted, suggesting end-stage disease and a poor prognosis. Biopsy from a masticatory muscle would be required to determine the degree of fibrosis, population of remaining type 2M fibers, and subsequent prognosis, but this was declined.\nThe cat was lost to follow-up until 1 year after initial presentation. At this time the cat was presented to the emergency service with a recent history of vomiting, anorexia and nasal discharge. Corticosteroid therapy had been discontinued 10 months previously. The cat was alert with appropriate behavior. Body condition score was 5/9 (4.3 kg). Body temperature was 40.3°C (104.6°F) and a bilateral purulent nasal discharge was evident. vmROM remained restricted at 11–12 mm. Thoracic radiography was unremarkable. A SNAP FeLV/FIV ELISA assay (IDEXX) was negative. After 18 h of supportive treatment, body temperature remained elevated at 40.7°C (105.3°F), and severe nasal discharge and anorexia persisted. The owners elected euthanasia on welfare grounds and approved post-mortem examination to further investigate MM.\nHead CT was performed post mortem using contiguous 2.0 slice thickness with 0.1 incremental helical slides using an ultra sharp bone algorithm (Somatom, 16 slice; Siemens). It revealed pronounced bilaterally symmetrical atrophy of the masticatory muscles with no radiographic abnormalities of the temporomandibular joints or other bony structures that would restrict mouth opening ().\nSpecimens were collected from the right and left temporalis and masseter muscles, and the biceps femoris muscle, fixed in 10% neutral buffered formalin, then evaluated at the Comparative Neuromuscular Laboratory (CNL), University of California San Diego. All of the temporalis and masseter muscles exhibited similar pathological changes (). Myofiber loss and fibrosis was marked with multifocal areas of lymphocytic infiltration having an endomysial and perimysial distribution. Large nodules of lymphocytic infiltration were focally present. The biopsy from the biceps femoris muscle was normal in appearance, without obvious cellular infiltration or fibrosis, supporting the focal nature of this inflammatory myopathy and making a generalized disorder such as polymyositis unlikely. The pathologic diagnosis was severe and end-stage inflammatory myopathy myositis with extensive fibrosis in all masticatory muscles evaluated. As in dogs, inflammation restricted to the masticatory muscles and the positive serum 2M antibody titer confirmed the diagnosis of MM in this cat.
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).