Craniomandibular Osteopathy with a Unique Neurological Manifestation in a Young Akita
This report describes a 4 mo old intact male Akita that presented for evaluation of a life-long history of facial swelling and failure to thrive. Physical examination revealed an enlarged cranium with prominent bony swellings on the maxillary bone, excessive laxity and crepitus involving multiple joints, and proprioceptive deficits. Radiographs demonstrated multiple osseous abnormalities including endosteal thickening of the femurs and ilium. Necropsy revealed gross compression of the cerebellum and brainstem. Physical exam findings, radiographic abnormalities, and histopathology of multiple boney lesions were all consistent with craniomandibular osteopathy. In this unique case of craniomandibular osteopathy, the dog was affected with severe bony proliferations leading to generalized hyperostotic lesions and brainstem compression resulting in neurologic deficits.
Introduction
Craniomandibular osteopathy (CMO) is a proliferative, non-neoplastic disease of dogs that usually affects the bones of the cranium.1 CMO was first described in the West Highland white terrier in 1958 and is now widely recognized in the terrier group.2 CMO has also been described rarely in other breeds. This case report describes a young Akita with neurologic deficits secondary to CMO, diagnosed based on clinical, radiographic, and histopathologic findings.
Case Report
A 4 mo old male intact Akita presented to the veterinary teaching hospital for a life-long history of facial swelling and failure to thrive (Figure 1). The owner (and breeder) first noticed abnormal growth patterns at 4–6 wk of age which progressed to significant facial swelling and appendicular orthopedic abnormalities. Two weeks prior to presentation, the owner also noted that the dog began to scuff his toes when walking and appeared less coordinated when moving. The only oral medication that the dog had received since birth was an unknown antibiotic prescribed for an upper respiratory infection. The owner had administered four vaccines and the dog was eating a commercial brand puppy food. No abnormalities were noted in any of the patient's six littermates.
Citation: Journal of the American Animal Hospital Association 47, 1; 10.5326/JAAHA-MS-5464
On presentation, the patient was bright, alert, responded to tactile stimuli, and had normal mentation for a 4 mo old puppy. The puppy weighed 12.5 kg, had a temperature of 38.6°C, a pulse rate of 98 beats/min, a respiratory rate of 36 breaths/min, and a body condition score of 3.5 out of 5. His eyes and ears were clear and his heart ausculted normally with no murmurs or arrhythmias noted. The puppy was unresponsive to audible stimuli, was bilaterally cryptorchid, had generalized palpable lymphadenomegaly, and increased bronchovesicular lung sounds were ausculted on both inspiration and expiration.
An orthopedic examination revealed an enlarged cranium with prominent bony swellings (3 cm to 4 cm in diameter) on the maxillary bone caudodorsal to the canine teeth and overlying the roots of all four carnassial teeth (Figure 2). Crepitus with mild discomfort was noted bilaterally in the elbows, shoulders, coxofemoral joints, stifles, and tarsi. A decreased range of motion was noted on manipulation of both carpi. Bilateral grade 1 medial patellar luxations were noted. The sternum was flattened with near 90 degree angles at the costochondral junctions.
Citation: Journal of the American Animal Hospital Association 47, 1; 10.5326/JAAHA-MS-5464
A neurologic examination revealed a mild proprioceptive ataxia with proprioceptive placing and hopping deficits in all four limbs. Spinal reflexes and the full cranial nerve exam, except for the dog's lack of response to audible stimuli, were appropriate for a 4 mo old puppy. No neck or spinal pain was elicited on palpation. The neurologic exam findings indicated that the neurologic lesion localization was intracranial but cervical localization could not be ruled out based on these findings.
The differential diagnoses included: CMO or some other congenital growth deformity; growth hormone deficiency; hypothyroidism; lysosomal storage disease; and neoplasia. To further evaluate the patient, diagnostics such as a CBC, chemistry profile, urinalysis, multiple radiographs including the skull and various long bones, and advanced imaging of the skull were recommended.
A CBC, chemistry panel, urinalysis, and a thyroid panel were performed. The CBC showed a normochromic, microcytic anemia with a PCV of 31.4% (reference range, 36.6%–59.6%). The chemistry profile revealed a decreased blood urea nitrogen of 7 mg/dL (reference range, 10–30 mg/dL), a hypoproteinemia of 4.9 g/dL (reference range, 5.2–7.3 g/dL), an elevated ALP of 272 U/L (reference range, 77–120 U/L), a hyperglycemia of 123 mg/dL (reference range, 77–120 mg/dL), a hypercalcemia of 11.6 mg/dL (reference range, 9.3–11.4 mg/dL), and a hyperphosphatemia of 9.4 mg/dL (reference range, 3.2–5.4 mg/dL). On urinalysis, the urine specific gravity was 1.023 with normal sediment. Thyroid panel results were normal with a thyroxine level 1.2 μg/dL (reference range, 0.73–2.0 μg/dL) and a thyroid stimulating hormone of 0.07 ng/mL (reference range, 0.02–0.32 ng/mL).
Radiographs were performed to further evaluate the abnormal musculoskeletal findings noted on physical exam. A smoothly marginated cortical thickening and periosteal proliferation of the maxilla and cranium were noted as well as essentially nonexistent tympanic bullae, frontal sinuses with no aerated opacity, and a moderately thickened soft palate (Figure 3). Radiographic findings of the appendicular skeleton included bilateral focal endosteal thickening/proliferation of the femur and humerus, the mid-diaphysis of the left tibia, the left antebrachium, and the right ulna, and the medial aspect of both ilial bodies. These osseous changes were suggestive of skeletal hyperostosis.
Citation: Journal of the American Animal Hospital Association 47, 1; 10.5326/JAAHA-MS-5464
Advanced imaging with CT in addition to urine metabolic screening tests to rule out amino acid, carbohydrate, and glycosaminoglycan disorders were recommended to further evaluate the lesions; however, the owner declined further diagnostic testing due to financial constraints.
Although CMO had not been previously described in the Akita breed, it was suspected in this case due to the physical examination, laboratory, and radiographic findings. Due to the severity in this case, a grave prognosis, and lack of effective treatment options, the patient was discharged from the hospital without treatment. The patient was found deceased at the owner's home 128 days after the original presentation. The owner remarked that the patient had remained mentally appropriate; however, he appeared to have significant respiratory difficulty during the 1–2 wk prior to his demise. The body was donated to the veterinary teaching hospital for necropsy.
At necropsy, large, firm, expansive masses were noted on the mandible and areas of the occipital, parietal, frontal, temporal, and maxillary bones of the skull. The cerebellum and brainstem were compressed and diverted ventrally due to the gross enlargement of the occipital bone (Figure 4). Markedly thickened cortical bone and subperiosteal woven bone and no evidence of neoplasia were noted on histopathologic analysis of the lesions in the skull and tibia. Bony trabeculae had scalloped edges, were composed of a mixture of woven and lamellar bone, and contained numerous resting and reversal lines. These histologic changes were consistent with CMO in reported cases.3 The histologic abnormalities were not consistent with hypertrophic osteodystrophy in the tibia or ribs diminishing the possibility of the two diseases existing concurrently in this patient. Histopathologic changes of the central nervous system included mild, multifocal myelin sheath and axonal swelling in the brainstem most consistent with a compressive lesion (Figure 5).
Citation: Journal of the American Animal Hospital Association 47, 1; 10.5326/JAAHA-MS-5464
Citation: Journal of the American Animal Hospital Association 47, 1; 10.5326/JAAHA-MS-5464
Discussion
CMO is a bilateral, irregular, non-neoplastic, osseous proliferative disease of dogs that usually affects multiple bones of the cranium.1 The condition was first described in the West Highland white terrier in 1958 and has since become widely recognized in the terrier breed.2 A recent publication investigating epidemiologic cases of developmental orthopedic diseases cited Cairn terriers, Scottish terriers, and West Highland white terriers as having an increased risk of CMO.4 This disease has also been described in other breeds, including Great Danes (n=2),5,6 Doberman pinschers (n=2),6 a boxer (n=1),7 an English bulldog (n=1),8 Labrador retrievers (n=3),6,9 Pyrenean mountain dogs (n=2)10 German shepherds (unknown number),6 a bullmastiff (n=1),11 a border collie (n=1),6 golden retrievers (n=3),6 a basset hound (1),6 a Catahoula (1),6 a German wirehaired pointer, (1)6 a Weimaraner (n=1),6 and Irish setters (n=2).1 The sporadic occurrence of this disease in larger breed dogs suggests that other etiologic factors may be involved with its transmission.12
CMO has been compared with Paget's disease and human infantile cortical hyperostosis which are proliferative bone disease of humans.13–15 Due to the histological similarity between Paget's disease and CMO, similar etiologies have been proposed such as a paramyxovirus (possibly CDV) infecting the osteoclastic cells.1 CDV has been detected in bone cells of dogs with hypertrophic osteopathy and distemper but no direct correlation has been linked with either an active distemper infection or vaccination with the development of CMO.1,16,17 CMO has been compared with human cortical hyperostosis due to the similar age of onset, radiographic findings, and histopathological progression.15 Unlike cortical hyperostosis in humans, which has an autosomal dominant gene of inheritance, CMO has been shown to have an autosomal recessive mode of inheritance in West Highland white terriers and a hereditary predisposition in Scottish terriers.18
As in this case, owners most often notice clinical signs of CMO in dogs less than 1 yr of age. Main clinical signs include moderate amounts of pain, difficulty with prehension, generalized facial swelling, and excessive drooling. Pain and difficulty with prehension may be absent in large breeds.1 On physical examination, affected animals generally have bony swelling associated with their mandible, maxilla, and calvarium. The Akita in this case had bony swellings associated with the maxilla caudodorsal to the canine teeth and overlying the roots of all four carnassial teeth and within areas of the calvarium consistent with CMO. Metabolic causes, such as hypothyroidism, could not be found that would explain the other bony changes in this patient due to the normal thyroid screen.
Diagnostic tests for CMO usually consist of a CBC, chemistry profile, urinalysis, and radiographs. Hematology and urinalysis results are usually unremarkable. The patient described herein had an elevated ALP and hyperphosphatemia, both of which have been associated with CMO; however, these changes can also be seen in normal, growing puppies.1,7,10 The mild anemia in this case was attributed to the age of the patient since puppies can have a mild anemia until 20 wk of age. The decreased blood urea nitrogen seen in this patient can be observed in younger animals due to increased fluid intake, increased urine output, and a higher anabolic state of rapid growth. A lower total protein, as in this case, can be seen in younger animals, which will normally increase to adult levels within 1 yr of age. The hyperglycemia and hypercalcemia were slightly outside of the reference range and considered insignificant. An ionized calcium could have been performed to further evaluate the calcium concentration in this patient.
Radiographic bony proliferations that are consistent with CMO are usually bilateral and symmetric. The majority of the radiographic changes associated with CMO involve the mandible but in 51% (n=45) of the cases in a review by Watson et al. (1995) involved both the tympanic bulla-petrous temporal bone area and mandible.1 In some instances, the bony changes can be confined to just the mandible or tympanic bulla-petrous temporal bone area,19 or they can involve other bones of the cranium.1 In this case report, the bony changes were periosteal proliferation of the cranium and maxilla which have been previously reported.14 In large breed dogs, as in this case, the affected bones are usually the mandibles. In one reported case, the temporomandibular region was also affected.7 In this case, the Akita not only showed radiographic changes in the bones of the cranium, but also the long bones. Radiographs of the long bones revealed focal endosteal proliferation on both femurs and humeri and the mid-diaphysis of the left tibia, right ulna, and left antebrachium (Figure 6).
Citation: Journal of the American Animal Hospital Association 47, 1; 10.5326/JAAHA-MS-5464
To the authors’ knowledge, generalized long bone involvement has not been previously reported in dogs with CMO; however, isolated long bone involvement of the radius and ulna, femur, and ulna alone have been described in multiple West Highland white terriers. One case with an enlarged ulnar and fibular diaphysis has also been reported.20 Long bone involvement has also been described in one Scottish terrier involving the ulna14 and in one Pyrenean mountain dog involving the radius and ulna.10 Some clinicians attribute the long bone proliferative lesions as an extension of the CMO while others contribute the lesions to hypertrophic osteodystrophy due to the radiographic similarities in the appearance of the metaphyseal region.12 Radiolucent (double physeal) lines consistent with hypertrophic osteodystrophy were not observed on the radiographs in the Akita described in this case.
No other CMO case appears to have been reported that describes neurologic deficits. The Akita in this case had proprioceptive deficits in all four limbs which were attributed to the CMO. On necropsy, no gross cervical lesions were observed and the severity of the bony proliferation in the skull resulted in compressive lesions on the caudal portion of the brain. Ambulatory tetraparesis may be caused by either focal diseases of the spinal cord and brainstem or generalized pathologic processes of the peripheral nervous system.21 Animals that are diagnosed with CNS lesions are ataxic and have conscious proprioceptive deficits and decreased postural reactions in all four limbs.21 It is possible that as the bony proliferations grew in size in the Akita described herein, a chronic compressive lesion resulted. The gross and histologic changes within the brainstem of the Akita correlate with the clinically observed neurologic deficits.
There are currently no standardized treatment protocols for CMO and no therapy was instituted in this case at the owner's request. Some authors advocate treatment with corticosteriods or a NSAID to reduce the inflammation and pain associated with this condition. Radical surgeries, such as a rostral hemimandibulectomy, have been performed to allow patients the ability to ingest nourishment; however, these surgeries are palliative at best and are clearly not a definitive cure for this disease.1 Prognosis for this disease is usually guarded when the bony lesions involve the temporomandibular joint because the lesion can eventually prevent prehension resulting in death without medical intervention. Owners usually elect humane euthanasia due to the poor prognosis of this disease.
Conclusion
This case was not only unique in the represented breed, but also the neurologic deficits observed on physical examination that have not previously been described in association with CMO. In addition, long bone involvement, which has historically only been described in the West Highland white terrier, has not been identified in any large breed dogs other than the one Pyrenean mountain dog. Although genetic testing and urine metabolic screening would have been helpful to rule out an underlying lysosomal storage disease or other cause of the observed abnormalities, these tests were not needed for a diagnosis of CMO in this case. In addition, gross examination of the cervical spine indicted no gross abnormalities but histopathological examination would have been helpful to rule out any underlying cervical disease. Future genetic research through microarray analysis may identify a genetic etiology for this disease to aid in the diagnosis of affected animals and identification of potential carriers of a genetic mutation.
A 4 mo old Akita is shown with an abnormally shaped and enlarged maxilla.
A 4 mo old male Akita presented with prominent bony swellings on the maxillary bone caudodorsal to the canine teeth and overlying the roots of all four carnassial teeth.
A: Right lateral radiograph of the skull of the 4 mo old Akita. Marked cortical thickening and periosteal proliferation involving the maxilla and the cranium are present. The tympanic bullae and frontal sinuses are obliterated by the hypertrophic bone. B: The ventrodorsal view of the skull shows bilateral periosteal proliferation of the mandible.
A sagittal postmortem view of the cranium just lateral to the midline reveals the brainstem and cerebellar compression from the boney proliferation. The large black arrow indicates the cerebrum, the large white arrow indicates the cerebellum, and the smaller black arrows indicate the gross enlargement of the occipital bone.
Histopathology of the brainstem. The arrow is pointing to a swollen axon and the arrowhead points to a dilated myelin sheath consistent with a compressive lesion.
Ventrodorsal view of the pelvis showing bilateral focal endosteal thickening or proliferation of the femur and endosteal proliferation of the medial aspects of each of the ilial bodies.
Contributor Notes
