Use of MRI for the Early Diagnosis of Masticatory Muscle Myositis
The medical records of two dogs that were diagnosed with masticatory muscle myositis (MMM) were reviewed. The reported clinical signs included intense pain when opening the mouth and restricted jaw movement. MRI detected widespread, symmetrical, and inhomogeneously hyperintense areas in the masticatory muscle. Electromyography (EMG) demonstrated severe and spontaneous pathologic activity in the temporal and masseter muscles. With early therapeutic treatment, remission of symptoms occurred within 2 mo, and no relapses were observed for the subsequent 2 yr. The gold standard for the diagnosis of MMM is the 2M antibody test, but the purpose of this study was to evaluate the use of MRI as an accurate and efficient diagnostic tool for the initiation of early therapy for the treatment of muscle myositis.
Introduction
Masticatory muscle myositis (MMM) is an inflammatory focal myopathy of autoimmune origin. It exclusively affects the masticatory muscles (i.e., temporal, masseter, pterygoideus, and rostral digastricus muscles). All of the muscle bellies of those muscles are innervated by the mandibular branch of the trigeminal nerve.1,2 MMM generally consists of two phases. The acute phase is characterized by edema, swelling, and pain in the masticatory muscles with restricted jaw movement (trismus). Conversely, the chronic phase is characterized by marked muscle atrophy due to the decreased size of the muscle fibers that leads to fibrosis. The chronic phase may evolve to severe muscle atrophy and the alteration of normal mouth movements.1,2
Similar to other myopathies, early diagnosis and treatment of MMM improves the clinical prognosis.3–6 Clinical examination, laboratory tests (hematologic, biochemical, and serologic), electromyography (EMG), histopathology, and imaging (including computed tomography and MRI) have been described for the diagnosis of MMM.1–4,7 Even today, MRI is still considered an optional and expensive tool for the diagnosis of myopathies in veterinary medicine. This technique can generally detect nonspecific inflammatory patterns, but its use is not well documented in the literature. On the contrary, in human medicine, MRI is a complementary tool for the early diagnosis of myopathies, evaluating the location and extent of disease, identifying the best site for biopsy, and verifying the efficacy of therapeutic procedures.3 The purpose of this study was to evaluate the use of MRI for the early diagnosis of MMM with the goal of prescribing treatment as soon as possible to obtain a favorable prognosis.
Case Report
Case 1
A 3 yr old female German wirehaired pointer weighing 32 kg was examined because she was unable to eat. The owner reported an acute onset with progressive worsening of her status. The referring veterinarian did not prescribe any therapy before referring the dog. Physical examination at the time of referral revealed pain when the masticatory and temporal muscles were palpated, inability to open the mouth, and dysphagia. Furthermore, bilateral and symmetrical swelling of the masticatory muscles was recognizable. No other major abnormalities were found, and the neurologic exam was normal. The complete blood count (CBC) did not reveal any abnormalities. Serum biochemical abnormalities included an increase in creatine kinase ([CK] 3.84 μkat/L; reference range, 0–2.17 μkat/L), which is normally increased in cases of muscular diseases. The thoracic and abdominal radiographic findings were normal, and serologic tests did not yield positive results (Toxoplasma IgG and IgM were both < 1:30 and Neospora and Leishmania immunofluorescence were both < 1:25).
Case 2
A 9 mo old female mixed-breed dog weighing 12 kg was examined by the referring veterinarian because of dysphagia. An unknown nonsteroidal anti-inflammatory drug was prescribed, but no improvement was seen. On presentation to the authors’ facility, the dog was unable to open her mouth > 2 cm, and intense pain in the masticatory muscles when opening the mouth was evident. Bilateral and symmetrical swelling of the masticatory muscles was also evident. No other major abnormalities were found, and the neurologic exam was normal. The results of the CBC indicated mild microcytosis (59 fL; reference range, 60–77 fL). Serum biochemical abnormalities included a slight increase in alkaline phosphatase (3.21 μkat/L; reference range, 0–2.67 μkat/L), aspartate aminotransferase (4.19 μkat/L; reference range, 0.17–0.75 μkat/L), alanine aminotransferase (1.32 μkat/L; reference range, 0.17–1.17), blood urea nitrogen (37.48 mmol/L; reference range, 6.43–17.85 mmol/L), triglycerides (1.41 mmol/L; reference range, 0.24–0.98 mmol/L), and CK (8.02 μkat; reference range, 0–2.17 μkat/L). The authors initially suspected hepatic and renal dysfunction related to the previously administered nonsteroidal anti-inflammatory drug, not muscle pathology. The dog underwent an abdominal ultrasonographic examination, but it did not highlight any abnormalities in the hepatic and renal parenchyma. Urinalysis, urine culture, and bile acid tests were normal. The thoracic and abdominal radiographs were normal, and serologic tests did not yield positive results (Toxoplasma IgG and IgM were both < 1:30 and Neospora and Leishmania immunofluorescence were both < 1:25).
Diagnostic Procedures
Both dogs underwent similar diagnostic procedures. After the clinical and neurologic examinations, blood tests (CBC and biochemical tests) and thoracic and abdominal radiographs, the dogs underwent MRI examinations of the head and neck, EMG examinations of the masticatory, tongue, and neck muscles, and temporal muscle biopsies.
The left and right frontal and masseter muscles and tongue muscles were evaluated via EMGa in both animals. MRI was performed using a 0.2 Tesla open magnetb. The adopted protocol included T2-weighted spin-echo (with the repetition time [TR]/echo time [TE]/number of acquisition [NEX] of 3,500/110/1) and T1-weighted spin-echo sequences (with the TR/TE/NEX of 800/26/3), both before and after IV administration of the contrast agent (0.5 mmol/mL gadolinium dimegluminec), along all spatial planes. Gradient-echo short T1 inversion recovery (GE STIR) sequences (with a TR/TE/NEX of 1,200/25/2; typically at a 90° flip angle) were used along the axial planes.
The differential diagnoses included generalized and focal myopathy, traumatic injury (e.g., temporomandibular luxation, mandibular fracture), a lesion in the retrobulbar space, trigeminal nerve disease, and other causes of trismus (e.g., tetanus, muscular dystrophy, foreign bodies, mandibular osteopathy).1 The authors also suspected MMM. Clinical and neurologic examinations were used to confirm localized problems and rule out the other differential diagnoses.
The EMG examinations demonstrated severe and spontaneous pathologic activities (fibrillations and positive sharp waves) in the temporal and masseter muscles. Conversely, no pathologic activities were observed in either the tongue or skeletal muscles of the limbs. The EMG findings were consistent with MMM and various neuropathic disorders; however, the absence of muscle atrophy and the acute clinical signs excluded neuropathy. The normal nerve conduction velocities of the ulnar, tibial, and peroneal nerves excluded polyneuropathic disorders. In addition, the EMG findings in the other muscles were normal, confirming that polymyositis was not present.
In both animals, MRI detected widespread, symmetrical, and inhomogeneously hyperintense areas in the masticatory muscles (temporal, masseter, medial and lateral pterygoid, and rostral digastricus muscles) using T2-weighted and GE STIR sequences. The T1-weighted sequences showed hypointense areas between the above-mentioned muscles and the other muscle bellies in the examined regions (e.g., longus of the head and geniohyoideus muscles; muscles of the cervical column; brachiocephalicus, sternocephalicus, and rhomboideus, multifidus of the neck, and longus of the neck muscle; and the other appendicular muscles) as shown in Figures 1, 2.
Citation: Journal of the American Animal Hospital Association 49, 5; 10.5326/JAAHA-MS-5915
Citation: Journal of the American Animal Hospital Association 49, 5; 10.5326/JAAHA-MS-5915
The T1-weighted sequences that were obtained after the administration of the contrast agent detected intense and inhomogeneous enhancement of the masticatory muscles, but the other muscle bellies were normal (Figure 3).
Citation: Journal of the American Animal Hospital Association 49, 5; 10.5326/JAAHA-MS-5915
Inflammatory myopathy (e.g., immune-mediated, infectious myositis) and infiltrative neoplasia were considered. To distinguish between those two diagnoses, a muscular biopsy was performed. The biopsy site was chosen based on the MRI images, and the temporal muscle was selected in both animals. That muscle was chosen because MRI indicated abnormalities in the temporal muscles, and the center of the temporal muscle was biopsied because the authors suspected a correlation with myopathy. The biopsy was performed in both animals using a simple surgical procedure.1 In both cases, two types of specimens were collected: one sample was fixed in 10% buffered formalin and the other was placed in sterile saline solution. The histologic examinations revealed signs of MMM, including inflammatory infiltrates with a multifocal distribution (mostly macrophages, lymphocytes, sporadic eosinophils, and plasma cells). Those infiltrates were associated with severe perimysial and endomysial fibrosis that had destroyed the structure of the normal muscle. A few residual muscle fibers presented with polymerism, necrosis, myophagocytosis, and regeneration.
Treatment was prescribed on the basis of the MRI and EMG findings. Immunosuppressive therapy was initiated that consisted of corticosteroidsd (2 mg/kg q 12 hr) in combination with antibiotic therapy (12.5 mg/kg clindamycine q 12 hr). Treatment was initiated while the serological results were still being processed. The histologic and serological findings definitively ruled out other kinds of myositis. Corticosteroids were administered at an immunosuppressive dosage and continued until remission of the acute phase (about 15 days). The dosage was progressively tapered and then discontinued after 2 mo. Although 2 mo of therapy is a short duration in comparison with other studies in the literature, including one study that suggested treating for 6 mo or longer, in these cases, complete remission of symptoms was observed within 2 mo and no relapses were observed after 2 yr of follow-up examinations.
Clindamycin was chosen because of its activity against the most frequent agents of infectious myositis (Toxoplasma and Neospora). It was administered until a complete positive response was noted on serological and histologic testing (20 days).
Discussion
MMM is an immune-mediated focal inflammatory myopathy. This condition exclusively affects the masticatory muscles, and the appendicular muscles are generally excluded.1 Although all of the masticatory muscles are composed of type 1 and 2 fibers, the appendicular muscles consist of type 1A fibers (slow-contraction fibers) and type 2A fibers (fast-contraction fibers). Conversely, masticatory muscles are composed of a variety of type 1A and 2M fibers, the latter of which are localized only in the masticatory muscles and are composed of a different isoform of myosin. Autoantibodies develop in 2M fibers during myositis; however, it remains unknown what initiates the formation of autoantibodies or why they are specifically directed against 2M fibers.1–4,8–11 The aforementioned myopathy is clinically characterized by trismus (restricted jaw movement) and dysphagia (pain and difficulty in swallowing), as well as painful and swollen masticatory muscles during the acute phase. Atrophy and fibrosis of the masticatory muscles are the typical clinical symptoms of the chronic phase, eventually resulting in the inability to swallow. Other associated clinical signs include exophthalmos, regional lymphadenopathy, and hyperthermia.1–3,5 Because of those reasons, it is important to make an early diagnosis.1,2
Although there are specific clinical signs, a diagnosis of MMM requires some diagnostics to be performed, such as hematologic, biochemical tests (including CK), and serological exams; 2M antibody tests; and (if necessary), a muscle biopsy. The 2M antibody test is very useful for the diagnosis of MMM, is easy to perform, and has a high sensitivity (85–90%) and specificity (100%).1,11 False-negative responses are always possible, especially in animals that have either been previously treated with corticosteroids or those in the end phase of the disease.
Further diagnostic tests, including EMG and advanced imaging techniques such as MRI, should also be considered. MRI is an advanced technique that provides accurate images of the muscular structures and is useful for recognizing diseases; however, nonspecific tomographic patterns often do not permit distinctions to be made between necrotic and inflammatory myopathies and infectious and immune-mediated diseases.4,12
In human medicine, MRI is a complementary tool for the early diagnosis of inflammatory myopathies. In veterinary medicine, the use of MRI for investigating inflammatory myopathies is rarely reported.8 Nevertheless, the utility of MRI for evaluating the extent and intensity of pathologic processes and choosing the best biopsy site is widely recognized.8 In addition, MRI may be used on follow-up examinations to monitor the evolution of lesions and verify the efficacy of treatment.4,8
Regardless, the gold standard for the diagnosis of MMM is still the 2M antibody test.1,9 Histologic examinations are useful, but they do present some limitations. First, the biopsy site could be incorrect because inflammatory processes are not homogeneously distributed and, consequently, false-negative results could result. Second, specificity depends on the stage of the disease. In the acute phase, inflammatory cells could be absent, while in the chronic phase, advanced fibrosis may prevent the disease from being recognized at all.10 In the latter case, MRI could be a good diagnostic tool because it allows the acute phase to be distinguished from the chronic phase. MRI also simplifies the decision-making process for choosing the best biopsy site, consequently lowering the number of false-negative results.4
Unfortunately, it takes time to obtain the results using histology and the 2M antibody test, and this is a problem that affects favorable prognosis by delaying early diagnosis and treatment. The goal is to have a test that sufficiently and accurately allows an early and clear diagnosis to be made. In this study, the authors’ goal was to demonstrate that MRI is a good test, especially the use of particular sequences. GE STIR sequences are highly sensitive to inflammatory processes. Consequently, those sequences allow an accurate diagnosis to be made and the early initiation of treatment while waiting for definitive histologic and serological results (e.g., the 2M antibody test). The entire MRI protocol used in this study consisted of T2- and T1-weighted sequences, along the three-dimensional planes and postcontrast T1-weighted and GE STIR sequences along the axial planes. Edema and inflammatory signs typically present during the early stages of inflammation and can be detected as hyperintense signals on T2-weighted sequences. On the other hand, they present as either isointense or hypointense signals on T1-weighted sequences.4
The results of this study correlate with those reported in the literature.4–8 The MRI scans detected alterations in the muscle bellies, and the different MRI sequences allowed the identification of pathologic tissues. Evident hyperintense signals were detected on the T2-weighted and GE STIR sequences of the masticatory muscles (temporalis, masseter, pterygoideus, and digastricus muscles), which also appeared to be swollen. T2-weighted and GE STIR sequences demonstrated high selectivity for the inflammatory processes in the masticatory muscles, which appeared as hyperintense signals due to the edema-like fluid that typically presents in the early stages of inflammatory myopathic disorders. The hyperintensity was bilateral, symmetrical, and easily detectable in comparison with the other muscles in the region, which presented as isointense signals. The other muscles of the neck (longus of the head, brachiocephalicus, sternocephalicus, rhomboideus, multifidus of the neck, and longus and longissimus of the neck muscles) presented as either isointense or hypointense signals. Those signals were clearly visible in Figures 1 and 2.
MMM diagnosis was then confirmed by the EMG examinations, which showed both abnormal activities in the masticatory muscles and normal activities in the appendicular muscles. The T2-weighted images revealed the location and extent of the inflammatory process; however, the T1-weighted images did not reveal any alterations to the muscles other than size (nonspecific information). Postcontrast T1-weighted images revealed a moderate to intense increase in the affected muscles (Figure 3).
In the authors’ opinions, those sequences were sufficient to suspect MMM. Additional diagnostic information was provided by the specific short T1 inversion recovery (STIR) and GE STIR sequences. Those latter two sequences allowed the saturation of fat tissue resulting in better recognition of muscle structures, especially affected structures, thus providing further confirmation of the inflammatory process.4 The edema-like fluid that characterizes the early stages of inflammatory myopathic disorders causes prolongation of the T2 TR resulting in the affected tissues being registered as hyperintense areas on T2-weighted images.4 T1-weighted sequences, however, were also less sensitive for the detection of edema. T1-weighted images of edema were recognized as either isointense or slightly hypointense areas in comparison with healthier counterparts. Fat-suppressing sequences, especially STIR sequences, are a sensitive, specific, and rapid diagnostic test for inflammatory myopathy that allow the identification of muscle inflammation by suppressing signals from fat tissue. GE STIR sequences are similar to STIR sequences in terms of sensitivity and specificity for studying inflammatory myopathy. Nevertheless, GE STIR sequences are characterized by good spatial resolution with a high signal/noise ratio and the presence of minor artifacts. Furthermore, GE STIR sequences can generally be executed in a shorter period of time compared with STIR sequences. In human medicine, it has been clearly documented that STIR sequences demonstrate 97% specificity for the identification of inflammatory myopathy.3
In the cases described herein, the GE STIR sequences demonstrated more intense signals in the affected muscles than the postcontrast T1-weighted sequences. It was easy to distinguish between healthy and affected muscles using GE STIR sequences (Figure 1). The use of GE STIR sequences confirmed the authors’ suspected diagnosis and helped the authors choose the best biopsy site.
Based on the MRI findings, the authors were able to start treatment of MMM. In this article, the authors demonstrated that MRI can lead to the early diagnosis of MMM. T2-weighted and GE STIR sequences were, in the authors’ opinions, better for the investigation of the early stages of inflammatory myopathic disorder. Early diagnosis and treatment resulted in the complete remission of symptoms.
Conclusion
In human medicine, it is widely known that MRI is an important tool for diagnosing myopathies, but in veterinary medicine MRI is still underused and poorly used. In addition, the cost of MRI is still too high for use in veterinary medicine. The results obtained in this study confirmed the importance of some types of examinations, especially histopathologic examinations and the 2M antibody test for ensuring a correct diagnosis. Furthermore, the importance of MRI for the early diagnosis of MMM in dogs was also confirmed. MRI allowed the authors to rule out other diseases with comparable symptoms, such as the presence of foreign bodies, temporomandibular fracture/luxation, tumors, abscesses, and polymyositis. The use of GE STIR sequences revealed the inflammatory sites and permitted the distinction to be made between the acute and chronic phases of the myopathy. Furthermore, GE STIR indicated the best biopsy site, thus guaranteeing more accurate histologic results. In conclusion, MRI demonstrated a major utility for the diagnosis of MMM beyond the authors’ expectations. Nevertheless, the authors recognize the roles of histopathologic examinations and the 2M antibody test for ensuring a complete, accurate, and definitive diagnosis. In the authors’ opinions, some MRI sequences (e.g., GE STIR) can allow an early diagnosis to be made.
MRI showing a symmetrical and inhomogeneous hyperintensity in the masticatory muscles on T2 sequencing (white asterisks).
Gradient-echo short T1 inversion recovery (GE STIR) sequences allow the saturation of fat tissue, resulting in better recognition of the muscle structures, especially in affected tissues (white asterisks indicate unaffected muscles and black asterisks indicate affected muscles).
T1-weighted postcontrast sequences showing intense and inhomogeneous enhancement of the masticatory muscles (black asterisks).
Contributor Notes
