The muscles of mastication are responsible for essential motor functions such as chewing and biting. In patients with the inability to open the mouth, breathing may be negatively impacted due to airway patency issues and respiratory distress, especially in dogs with brachycephalic skull configuration (1). The masticatory muscles responsible for closing the mouth and elevating the mandible include the temporalis, masseter, medial pterygoid, and lateral pterygoid. The rostral belly of the digastricus is considered a complementary muscle of mastication and is responsible for opening the mouth. This action is supplemented by the lateral pterygoid, which helps to depress the mandible while opening. All of these muscles are innervated by the mandibular branch of the trigeminal nerve (CN V) with exception of the caudal belly of the digastricus muscle, which is innervated by the facial nerve (CN VII) (2).

Primary dysfunction of the masticatory muscles typically manifests as changes in jaw mobility (1). Trismus is a spasm of the muscles of mastication, resulting in inability to open the mouth (3). Conversely, mandibular paralysis or “dropped jaw” can manifest as an inability to close the mouth (4). Several systemic and localized disease processes may cause dysfunction of the masticatory muscles that present early on as difficulty in opening or closing the mouth with or without obvious pain (Table 1). If patients are not promptly and accurately diagnosed and treated, severe consequences may develop with some causing life-threatening sequelae (1). The goal of this review is to inform on the spectrum of masticatory muscles disorders, synthesize the current literature to assist clinicians in approaching these challenging cases, and highlight knowledge gaps that require further research.

Inflammatory myopathies are defined as those in which skeletal muscles contain infiltrates that are both cellular and nonsuppurative (5). In dogs, focal and generalized inflammatory myopathies have been recognized (5–9), and can be further categorized as immune-mediated, idiopathic, or secondary to infectious disease (9). The most common inflammatory myopathies of dogs that can affect the muscles of mastication are masticatory muscle myositis (MMM), polymyositis (PM), and generalized myositis from infectious disease (5). Extraocular myositis (EOM) and dermatomyositis (DM) are also inflammatory myopathies of dogs, but do not directly cause masticatory muscle dysfunction (6).

A canine Overlap Syndrome (OS) has also been reported in the literature in which dogs display clinical signs consistent with both PM and MMM. OS results in cellular infiltrates being found in limb muscles and masticatory muscles, a characteristic finding of PM, and also have positive 2 M antibodies (5). Additional research is needed to further explore the prevalence, severity, and prognosis of OS inflammatory myopathies.

The diagnostic workup for inflammatory myopathies includes laboratory work (complete blood count/chemistry panel), advanced diagnostic imaging, and muscle biopsy with histopathologic review. Bloodwork changes routinely include elevated creatine kinase (CK) due to myofiber necrosis (5). Severe myofiber necrosis in cases of inflammatory myopathies may also result in elevated levels of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) (9). A neutrophilia, secondary to leukocytosis, may also be present (10).

Advanced diagnostic imaging in the form of contrast computed tomography (CT) or magnetic resonance imaging (MRI) is prudent to assess the nature and extent of myositis (8–11). In inflammatory myopathy cases, muscles are initially inflamed and edematous, appearing enlarged and hypoattenuating on CT pre-contrast (11). After contrast administration, non-homogenous or heterogenous enhancement is detected due to the increased vascularity of inflammatory change (12). Areas that lack contrast enhancement can be present, which correspond to areas of muscle necrosis (11). MRI is superior in inflammatory myopathy cases when differentiation is needed amongst fat, fibrosis, cellular infiltrates, edema, and calcification (7). On both T1 and T2 weighted images, muscles affected by inflammatory myopathies are poorly marginated and diffuse, appearing hyperintense (8, 9). When contrast is administered, marked enhancement is noted in affected muscles and areas of necrosis do not have enhancement (Figure 1) (8).

Confirmatory diagnosis of an inflammatory myopathy is made through muscle biopsy with histopathologic detection of inflammatory change present (Figure 2) (7). Biopsy sites are determined based on localization of contrast enhanced areas in CT and MRI studies (8, 11).

Infectious causes of generalized myositis can be parasitic, bacterial, rickettsial, or fungal in origin (7). An important differentiating factor for dogs affected with infectious myositis is that they are more likely to display lower motor neuron weakness (5). In a review of 200 cases of inflammatory myopathies, 140 cases were determined to be generalized inflammatory myopathies and 28.5% of those were classified as infectious (5). A presumptive diagnosis of generalized myositis of infectious origin may be based on clinical signs and positive serology testing, but a definitive diagnosis requires organism identification through immunohistochemical or molecular means (7).

Parasitic etiologies are most commonly reported and include neosporosis, toxoplasmosis, leishmaniasis, hepatozoonosis, trypanosomiasis, trichinosis, sarcocystosis, and microfilariasis (6, 7). Of these, Neospora caninum is the most common parasitic cause of infectious myositis (6). Transmission occurs through ingesting tissues containing bradyzoites such as fetal membranes or placentas. Dogs can also be infected vertically through placental transmission of tachyzoites (41). Clinical signs of dogs with neosporosis include stiffness, muscle atrophy including the masticatory muscles, and myalgia. A vast majority of dogs will also exhibit polyradiculoneuritis and display characteristic pelvic limb hyperextension and rigidity. N. caninum may lead to atrophy through secondary denervation or radiculoneuropathy (6). MRI imaging of dogs affected with N. caninum shows bilateral and multifocal changes to masticatory muscles on T2 weighted and fluid-attenuated inversion recovery (FLAIR) images. Contrast administration causes enhancement of muscular lesions (42). Definitive diagnosis requires use of tissue aspirates or muscle biopsies to detect tachyzoites and bradyzoites, respectively. Although there is no approved treatment protocol for N. caninum, the following medications have been used for clinical control: clindamycin at 12–25 mg/kg PO q12h for 4 weeks or trimethoprim sulfadiazine 15–20 mg/kg PO q12h for 4 weeks with pyrimethamine at 1 mg/kg PO q24h for 4 weeks (Table 2) (41).

Toxoplasma gondii infections are highest in populations of dogs that consume raw or undercooked meat containing bradyzoites (7). Additionally, many cases of T. gondii infections have been reported in young, immunocompromised dogs with concurrent canine distemper viral infections (43, 44). Clinical signs are related to central nervous system dysfunction, but myopathic changes include myalgia, atrophy, stiffness, and inflammation (45). Similar to N. caninum, polyradiculoneuritis may also be present with hyperextension and rigidity of the pelvic limbs (46). Affected muscles may develop granulomatous inflammatory reactions that correspond to bradyzoites (7). Diagnosis may be performed through antibody assays and PCR tests through use of feces, fluid, or tissue (47). Successful treatment options that have been reported in the literature include clindamycin at 10 mg/kg PO q8h or trimethoprim sulfadiazine at 15 mg/kg PO q12h with pyrimethamine at 1 mg/kg PO q24h (46). Additionally, azithromycin at 10 mg/kg PO q24h has been used in cases of disseminated disease (Table 2) (47).

Infection with Leishmania has also been reported to cause masticatory and skeletal myositis in dogs (6, 7). A retrospective cohort study of 24 dogs diagnosed with leishmaniasis found a commonality of bilateral masticatory muscle atrophy and myalgia, yet normal jaw function (48). Additional clinical signs of systemic leishmaniasis include lymphadenopathy, weight loss, severe dermatitis, and weakness (7, 43). Dogs affected with leishmaniasis show myopathic changes including necrosis, fibrosis, and mononuclear cell infiltration (lymphocytes, histiocytes, and plasma cells) on histopathology reports (43). For a definitive diagnosis, identification of Giemsa-stained amastigotes is needed (48). The amastigotes are found within macrophages at site of infection and not within skeletal muscle fibers (49). There is a positive correlation between the quantity of amastigotes present and severity of disease and inflammatory change (43). The “classic” treatment option for canine leishmaniasis is a pentavalent antimonial, specifically meglumine antimoniate (Glucantime) (49). Meglumine antimoniate is dosed at 75–100 mg/kg SQ q24h for 4–8 weeks and allopurinol is dosed at 10 mg/kg PO a12h for at least six months (50). A second-choice treatment option is amphotericin B dosed at 0.1–1 mg/kg IV q24h or twice weekly for up to two months. More recently, the combination of miltefosine dosed at 2 mg/kg PO q24h with allopurinol dosed at 10 mg/kg PO q12h for six months has been described (Table 2) (51).

Trypanosomiasis (Chagas disease) caused by Trypanosoma cruzi affects skeletal and myocardial muscles in dogs. Disease progression can be acute or chronic (7). Acute manifestations of Trypanosomiasis can lead to rapid death due to myocarditis and arrhythmias. Chronic manifestations lead to severe cardiac changes such as dilated cardiomyopathy and eventually results in congestive heart failure (52). No current cases have been reported to affect canine masticatory muscles, but the potential is there. Definitive diagnosis requires the identification of trypomastigotes within a Wright’s or Giemsa-stained blood smear (7). Treatment can be challenging and complex in cases of Chagas disease. The use of congestive heart failure medications with amiodarone at 7.5 mg/kg PO q24h and itraconazole at 10 mg/kg PO q24h has been trialed (Table 2) (53, 54).

Canine sarcocystosis is rare, but it has been documented in a handful of case reports to cause generalized myositis (55, 56). A case report of two dogs in the United States reported clinical signs of fever, myalgia, muscle atrophy, and reluctance to move. Clinicopathology changes included increased ALT, lymphopenia, and thrombocytopenia. Muscle biopsies were taken and histologic examination revealed the presence of many sarcocysts and a necrotizing and inflammatory myopathy. Analgesics and clindamycin at 13 mg/kg PO q12h were initially prescribed for both patients; one dog eventually died and the other responded with the addition of decoquinate at 10–20 mg/kg PO q12h (Table 2) (55). Additional research is needed on the efficacy of decoquinate in canine sarcocystosis.

Bacterial diseases are much less common causes of infectious myositis, yet include leptospirosis and clostridial infections. Some cases of Leptospira australis and Leptospira icterohemorrhagiae infections have resulted in generalized myositis. Clinical signs observed in these cases are severe myalgia, fever, and difficulty walking (7). Supportive laboratory diagnostics include a Leptospira microscopic agglutination test (MAT) titer ≥ 800 or presence of IgM antibodies. Definitive laboratory diagnostics include at least a fourfold increase in the Leptospira agglutination titers from acute phase and convalescent phase samples. Treatment includes a two-week regimen of doxycycline at 5 mg/kg PO q12h (Table 2) (57).

Clostridial infections in myositis cases have been reported to cause severe myalgia (7). Infection introduction has been documented from penetrating wounds, intramuscular injection sites, and surgical contamination (57–59). Aggressive debridement and strain-specific antibiotic therapy is required in these cases (7). Infection specifically with Clostridium tetani will be discussed in more detail in the following section.

A rickettsial disease that has been reported to cause infectious myositis includes Ehrlichia canis, causing canine monocyte ehrlichiosis (7). Early on in ehrlichiosis, dogs have been reported with PM due the presence of muscle atrophy and cellular infiltrates being identified in muscle biopsies (6). Affected dogs can go through acute, subclinical, and chronic phases of disease (60). The acute phase is when dogs have been documented to develop myositis and clinical signs such as diffuse atrophy (7). Thrombocytopenia and anemia occur and cause pale mucous membranes to be present (60). Morula of E. canis are detected only 4–6% of the time, so additional testing through serology and PCR are required for diagnosis (61). Treatment consists of tetracycline antibiotics such as doxycycline at 5 mg/kg PO q12h or 10 mg/kg PO q24h for four weeks (Table 2) (62). Tick-borne diseases may also cause infectious myositis with similar clinical signs to N. caninum, including Hepatozoon canis and Hepatozoon americanum (6). Muscles biopsies of those with an infectious myopathy contain characteristic parasitic cysts (5).

In short, more than one test is typically required to diagnose an inflammatory myopathy and determine its etiology. This can range from any combination of serologic testing for infectious agents or autoantibodies, clinical signs, blood work, or muscle biopsy with immunophenotyping. MMM and PM can be differentiated by use of 2 M antibody titer testing and muscle biopsy. There is potential for diagnostic results to support both MMM and PM, in which OS may be present. Histologically, dogs with MMM typically have perimysial and endomysial fibrosis and infiltrates while dogs with PM have only endomysial fibrosis and infiltrates. Parasitic cysts can be identified in biopsies of cases with infectious myositis. Clearly, biopsy is key in the diagnostic workup of inflammatory myopathy cases (5).

Trauma affecting the muscles of mastication may result in contracted or swollen masticatory muscles further resulting in restrictive mouth opening (RMO). Other traumatic injuries can occur to the bones of the skull near the muscles of mastication and cause trismus as a secondary process.

Another potential consequence of masticatory muscle trauma is acute compartment syndrome (ACS). This is a rare musculoskeletal condition in which there is an acute increase in osteofascial compartment pressure (63). Multiple authors suggest that ACS develops when the pressure within the affected area nears systemic diastolic blood pressure (64, 65). If left untreated, it may cause ischemia and necrosis of the affected area (65), carrying a high morbidity rate (64).

Diagnosis of ACS can be challenging and is done on an emergent basis (65). Clinical diagnosis is dependent on the combination of clinical signs and measurements of intra-compartment pressures (64). Previous cases in veterinary literature have reported that pressures exceeding 30 mmHg require immediate fasciotomy (63). CT imaging of ACS in dogs reveals nonhomogeneous contrast enhancement and enlargement of affected muscles (66). Treatment for ACS involves emergency fasciotomy for surgical decompression (66). A review of ACS in human medicine indicated that the best prognosis occurs if surgery takes place within six hours of the inciting injury or traumatic event. After six hours, the chance of permanent nerve injury is increased. If necrotic tissue is present, debridement is necessary and there is an increased chance of infection (65).

Penetrating foreign bodies may also affect the muscles of mastication (Figure 3). A report on two dogs with oropharyngeal foreign bodies localized to the pterygoid muscle were diagnosed via CT. Both dogs had chronic histories (one year and five years, respectively) of discomfort and inability to fully open the mouth. CT imaging revealed asymmetric and contrast-enhanced regions of the pterygoid muscle (67). Similarly, another report documented an 8-year-old German shepherd with trismus and mouth pain for one month duration along with fever and temporalis muscle atrophy. MRI findings were supportive of myositis of both temporalis muscles, and a subcutaneous abscess was detected dorsal to the sagittal crest. It was suspected that the abscess was due to a penetrating injury from chewing on a stick (68).

Infection and abscess secondary to a stick chewing penetrating wound is typically treated with antibiotics such as amoxicillin-clavulanic acid (68). Alternatively, surgery may be pursued in trauma cases as needed if a foreign body is identified in the masticatory muscles or its proximity (67–72). Removal of pterygoid muscle foreign bodies and necrotic material was facilitated through a novel paramedian ventral mandibular approach in the report on two dogs (69).

Post trauma physical therapy to the craniofacial region is not yet well established in veterinary medicine. The main goal of physical therapy is to restore and maintain adequate range of motion and decrease fibrotic changes. Physical therapy sessions may involve massaging the affected muscles and then opening the mouth and holding that position for 20–30 s; the hold is then released and the exercise may be repeated (69). The authors have also discussed using OraStrech (CranioMandibular Rehab, Inc. Wheat Ridge, Colorado) to rehabilitate the jaws and masticatory muscles in various circumstances, but studies demonstrating its efficacy in dogs are currently unavailable (1). Also, implementing diet changes such as progressively larger kibble to encourage chewing can be utilized in the post-operative period (69).

MO is defined as non-malignant, heterotopic, metaplastic bone that develops within skeletal muscle (72). MO cases typically present with inability to open or close the mouth depending on the location and extent of mineralization. MO is subdivided into myositis ossificans progressiva (MOP) and myositis ossificans traumatica (MOT), which are differentiated by their pathophysiology and etiology (73, 74).

MOP is a rare hereditary disorder with a human prevalence of 1/2,000,000 reported (75). Historically, it has been described by several other names including Münchmeyer’s disease and “stone man syndrome” in humans (76). More recently, MOP has been referred to as fibrodysplasia ossificans progressiva (FOP) in all species (74).

The human inheritance pattern has been determined to be autosomal dominant and caused by a mutation in the Activin A receptor type 1 (ACVR1) gene, which encodes for Activin receptor-like kinase 2 (ALK2) receptor for bone morphogenic proteins (BMP) (75–77). Mutation of this gene in MOP patients results in dysregulation of BMP pathways (78), and ALK2 is involved in signaling pathways that regulate the formation of new bone, fracture healing, and embryology (76). Since the inhibitory protein for ACVR1/ALK2 is partially deleted in this mutation, ACVR1/ALK2 is active in the absence of BMP signaling (77). This leads to an overabundance of osteoblastic activity at the site of overexpression and development of MOP lesions that can be multifocal (76). The genetic basis of canine MOP has not been established and requires further research.

In humans, initial masticatory muscle involvement is not common in MOP but can occur with disease progression (76). A review of 42 human cases of MOP affecting the masticatory muscles found that the masseter is most commonly affected. This is followed by the medial pterygoid, lateral pterygoid, and temporalis in order of decreasing frequency of occurrence (79).

Cases in the literature of MOP or MOP-like lesions in dogs are rare and typically involve lameness and target the hip joint (80, 81). There are two individual case reports of canine MOP lesions developing within paravertebral muscles near the cervical spine (82, 83). One report described a neurogenic lameness of the left forelimb, which was the first reported case of canine MOP causing nerve compression (82). The other report did not describe any neurologic deficits (83). Currently, no cases have been described of MOP lesions within canine masticatory muscles.

MOT is a localized, idiopathic, heterotopic osseous lesion formed within soft tissue structures (84). It has also been described by several other names including traumatic myositis ossificans, myositis ossificans circumscripta, localized myositis ossificans, or fibrodysplasia ossificans circumscripta (85). Although no etiology has been agreed upon in human or veterinary medicine, some suspect MOT occurs in response to a traumatic injury that creates fibroproliferative change, forming mature endochondral bone (86). Further, it is hypothesized that BMPs modulate this response and are directly released from injured bones secondary to trauma (85). Other theories involve the notion of bony fragments translocating into nearby soft tissues following trauma, movement of subperiosteal osteoprogenitor cells, hematoma formation with secondary mineralization, or periosteal detachment and osteoprogenitor cell proliferation (87).

In human literature, proposed inciting injuries of MOT affecting the muscles of mastication include external traumas, tooth extraction complications, anesthetic injections, odontogenic infections, and burns (73, 88). In dogs, there is a single maxillofacial case report of MOT occurring in a 5-month-old female intact German shepherd after experiencing a dog bite wound below her right zygomatic arch (89). A majority of reported cases of canine MOT have been described in the triceps muscle, caudal thigh muscles, caudal cervical region, and extensor carpi radialis muscle following traumatic or concussive injuries (83, 90–92).

There is a suspected correlation between MOT and hemophilia in humans, specifically with Factor XI deficiency (80). Similarly, there is a proposed link between Doberman pinschers and the development of MOT-like lesions in the face of microvascular bleeding (80).

MO of the pterygoid muscles has been described in dogs and humans from both genetic and traumatic etiologies (1, 88, 93). If a genetic basis is not found, human causes of pterygoid mineralization are typically from traumatic events ranging from dental extractions to vehicular accidents (88). A small case series described two young French bulldogs with bilateral MO-like lesions within their pterygoid muscles, causing trismus. The history of both patients was unknown, so it was unclear if these were cases of MOP or MOT within the pterygoids (1). Another case report identified similar bilateral ossification in the area of the pterygoid muscles in an Airedale terrier, but it was not called MO. Instead, it was referred to as extracapsular soft tissue ossification (93).

The diagnostic workup for suspected MO cases includes blood work, advanced diagnostic imaging, and biopsy with histopathology (85). Bloodwork can rule out other systemic conditions that cause extra-skeletal ossification and should include assessment of phosphatase, parathyroid hormone, and calcitonin levels (87). Diagnostic imaging should include MRI or CT to fully assess maxillofacial structures and for early disease detection (73). When using MRI, both T1 and T2 weighted images of mature MO lesions appear hyperintense and similar to cancellous fat within affected muscles (82). On CT, MO appears as an ossified growth that has a zonal pattern with increasing radiopacity centripetally and a radiolucent center (73, 87). In pterygoid MO cases, common CT findings include osseous proliferation that bridges from the medial aspect of the caudal mandible to the tympanic bulla (Figure 4) (94).

Although imaging is typically suggestive of MO, definitive diagnosis is made through biopsy and histopathology (95). Histological changes consistent with MO have been described as a “zone phenomena,” meaning that there are three identifiable zones (inner, middle, and outer) (85, 94). The inner zone houses undifferentiated cells along with muscular tissue that can contain hemorrhagic and necrotic components. Mitosis can be detected in giant mesenchymal cells present in the inner layer. The middle zone includes immature osteoid and active osteoblasts. Woven bone tissue is also detected in the middle zone. Finally, the outer zone is where mature lamellar bone can be found with evidence of osteoclastic activity (85). Collectively, these findings indicate that osseous metaplasia or heterotopic mineralization has taken place (Figure 5) (94). In short, the clinical diagnosis of MO requires histopathologic detection of the progression from fibrous metaplasia to mature bone in affected muscles (1).

Clinically, it is important to distinguish MOP from MOT due to MOP having a worse prognosis (76). MOP cases are typically multifocal, so surveying other areas of the body for MOP lesions is recommended. Ultimately, MOP is a progressive and disabling disorder that typically leads to ankylosis and immobilization of affected soft tissue structures (75). Disease prognosis is poor with no current successful treatment options (76). Death is usually secondary to thoracic insufficiency syndrome (75).

Conversely, MOT is typically localized to a single area of the body and patients may have a history of traumatic injury (73, 94). Additionally, follow up with serial imaging, such as CT, may show that MOT lesions remain static with lack of progression (1).

Treatment options range from conservative management to surgical excision of ossified lesions (85). There is no definitive medical management for MO in humans or animals, and current medical management is aimed at reducing pain, optimizing function, and avoiding additional trauma (95). In humans, MO lesions and flare ups localized to the back or chest can be managed with cyclooxygenase-2 (COX-2) inhibitors, non-steroidal anti-inflammatories (NSAIDs), or muscle relaxants; MO lesions and flare ups of the limbs and jaw in humans can be managed with prednisone and muscle relaxants. Use of leukotriene inhibitors, mast cell stabilizers, and bisphosphonates have also been explored in human medicine but require more studies on their efficacy (95). Physiotherapy may be implemented in cases of conservative management (85). Future research is needed specifically for MOP treatment to target BMP signaling pathways mediated by ACVR1.

Thoughtful surgical planning is required for MO cases and timing of surgical intervention is controversial (1). It is believed that if surgery is performed while lesions are still developing during the acute or immature phase, then it could lead to more aggressive bone development and recurrence (74, 85). The acute phase of MO development can last two to six weeks and is followed by the mature phase in which complete ossification occurs over several months (96). Therefore, many authors support surgical intervention during the mature phase once lesion ossification is present; this allows for the lesion to be well delineated from skeletal muscles surrounding it (85). In severe cases, such as bilateral pterygoid mineralization, salvage procedures such as bilateral segmental mandibulectomy may be appropriate (1).

Recent research in human medicine has explored the use of peri- and post-operative radiation therapy in surgical management of MO cases and helping decrease recurrence rates. The current radiation therapy recommendation to decrease MO recurrence in humans is 7 to 8 Gray (Gy) in a single fraction 24 h before surgery or 48 h after surgery (97). If surgical intervention is not possible and conservative therapy is not effective, then euthanasia may need to be discussed. This is evident given poor patient welfare and potential for life threatening complications in severe cases of MO affecting the maxillofacial region and causing inability to open the mouth (1).

Tetanus is a neurologic disease caused by Clostridium tetani, a sporulating, anaerobic bacterium found in soils and characterized by a spastic paralysis (98, 99). C. tetani produces a neurotoxin termed the tetanus toxin (TeNT) along with a hemolysin known as tetanolysin (100). Tetanus infection may present as a localized or systemic form (101). Systemic (generalized) cases of tetanus start off with spasticity of the masticatory muscles, creating a “sarcastic grin” (also known as Risus sardonicus) appearance, ‘locking of the jaws’ and progressing to involvement of the trunk and extremity muscles (99).

The most commonly affected areas of the body are those that make contact directly with soil (100). Wound conditions that favor spore germination are anaerobic with necrotic tissue present and little access to air (101). Once a wound is contaminated with C. tetani, tetanus takes place when its toxin is released (100). The authors have also seen a fractured deciduous canine tooth that was the most likely nidus of infection (unpublished data).

At the site of infection, TeNT is exposed to local demyelinated nerve endings. Once TeNT is bound to its receptor (currently not known) it is transported to the central nervous system (CNS) to a neuronal cell body via retrograde axonal transport (102). Its final destination is inhibitory interneurons in the CNS that are responsible for coordinating motor nerve activity. TeNT then inhibits the release of gamma-aminobutyric acid (GABA) and glycine (103). When both of these molecules are inhibited, it leads to continued muscle contraction due to excessive motor neuron firing (100). Tetanospasmin also inhibits additional neurotransmitter release including acetylcholine (102).

A retrospective analysis of 18 cases of tetanus in dogs described that the first clinical signs involve localized maxillofacial changes such as trismus, dysphagia, vomiting, and risus sardonicus. Nearly 50% of infected dogs progress to display signs of systemic (generalized) tetanus. Clinical signs of progression involve muscle contractions that are tonic and prolonged in nature (104). Since voluntary muscles are targeted, clinically affected animals present with tetanic spasm and rigidity (101). Affected animals may also experience autonomic nervous system changes in which sweating, hypertension, and tachycardia develop and are followed by hypotension and bradycardia (100). The duration of clinical signs may be several weeks (101).

A retrospective cohort study of 53 cases of canine tetanus reported respiratory complications in 26.4% (14/53) of patients, including aspiration pneumonia and upper airway obstruction. A poor prognosis was associated with these patients and only 14.3% (2/14) survived. This was contrasted to dogs without respiratory complications in which 94.8% (37/39) survived to discharge (98).

Diagnosis of tetanus is initially presumed based on the presence of spastic paralysis +/− presence of a wound, as there is no current definitive antemortem lab test for tetanus (104). Early cases of clinical tetanus may be misdiagnosed as myopathies. In dogs, localized tetanus may also be diagnosed with use of EMG (101). Doublets and triplets will be recorded and are consistent with motoneurons that are hyperexcitable. Repeatability of EMG findings under general anesthesia is ideal for confirmation of motor neuron disease (102). If present, wound exudate may be used to isolate C. tetani for culture. C. tetani may lose its ability to pick up Gram coloration in Gram staining tests if the culture is greater than 24 h old. Finally, advanced diagnostic imaging in the form of MRI or CT typically reveals inflammatory change (102).

There is no specific treatment for active tetanus infections other than supportive care (100). Analysis of survival in a retrospective study of 42 cases found that young dogs (less than two years of age) with severe generalized disease and rapid progression have a guarded prognosis (99). Mortality ranges from 18 to 50% with higher rates in dogs with respiratory and autonomic complications (101).

Wound cleaning, debridement, and antibiotic therapy such as metronidazole at 10–15 mg/kg IV q8h are a priority in tetanus cases (Table 2) (100, 105). Tetanus antibodies can be utilized to stop unbound TeNT from continued binding, but it cannot prevent the action of TeNT that is already in the CNS (100). It is imperative to make sure patients are hospitalized in a location that is quiet, dark, well ventilated, and has minimal stimulation to prevent spasms (101). A few clinical case reports have used magnesium sulphate (MgSO₄) as an adjunct muscle relaxant in cases of canine generalized tetanus (106, 107).

Neoplasia is a differential that should also be considered in cases of masticatory muscle dysfunction. Neoplasms may restrict mouth opening directly by involving the muscles of mastication or indirectly by involving the temporomandibular joint, trigeminal nerve or its branches, other soft and osseous tissues, or by causing cancer cachexia (108).

Additionally, neoplasia typically leads to unilateral masticatory muscle atrophy and facial asymmetry. A neoplastic process may be localized to the trigeminal nerve such as a peripheral nerve sheath tumor (109). Other less common types of neoplasia that may affect the trigeminal nerve include lymphoma (4). Besides unilateral atrophy, affected dogs may also have neurologic deficits such as absent palpebral reflex, decreased menace response, loss of corneal sensation, ipsilateral Horner’s syndrome, and enophthalmia (109).

A retrospective cohort study of 64 cases of dogs with unilateral masticatory muscle atrophy reported that MRI was unable to localize a lesion, such as a tumor, in over 25% of cases. Preliminary discussion on this topic proposed that the lesions may be present but are too small to be detected on MRI. Additional studies are needed to support this notion and/or identify the pathology present in that group lacking a detectable discrete tumor (109).

This comprehensive review included multiple areas further research related to the diagnosis and treatment of masticatory muscle disorders in dogs. Diagnostic uncertainties include the limitation of MRI for detection of neoplasia. Additionally, the presence of an OS with characteristic findings of both MMM and PM creates another level of diagnostic uncertainty in these cases. Therapeutic uncertainties revolve around MMM and establishing a universally accepted protocol for starting immunosuppressive dosages of corticosteroids, tapering timeline, monitoring, and long-term management of refractory cases. The alternative use of dexamethasone, azathioprine, mycophenolate mofetil, leflunomide, cyclosporin, and JAK inhibitors for treatment of MMM also requires further research to establish efficacy. Finally, additional investigation is needed to determine the genetic basis of MOP in dogs along with the potential for targeted treatment at BMP signaling pathways.

Without a doubt, several differentials should to be thoughtfully considered in cases involving masticatory muscle dysfunction. Long term prognosis improves with early recognition, appropriate diagnostics, and targeted treatment. A working knowledge of the pathophysiology and etiology of these disorders allows for clinicians to more confidently approach cases involving masticatory malfunction. Additionally, rule out lists are fundamental in the diagnostic process of patients with a change in their mouth opening or closing. As previously established, empirically treating these patients with immunosuppressive medications can have devastating repercussions in the face of an undiagnosed infection. In short, thorough workup using advanced diagnostic imaging, biopsy, and targeted informed treatment are imperative for patients with masticatory muscle pathology due to potentially life-threatening consequences (Figure 6).