In the Stomatognathic System
Kazuya Yoshida
Abstract
Various movement disorders, such as oromandibular dystonia, oral dyskinesia, bruxism, functional (psychogenic) movement disorder, and tremors, exist in the stomatognathic system. Most patients experiencing involuntary movements due to these disorders visit dentists or oral surgeons, who may be the first healthcare providers. However, differential diagnoses require neurological and dental knowledge. This study aimed to review scientific advances in botulinum toxin therapy for these conditions. The results indicated that botulinum toxin injection is effective and safe, with few side effects in most cases when properly administered by an experienced clinician. The diagnosis and treatment of movement disorders in the stomatognathic system require both neurological and dental or oral surgical knowledge and skills, and well-designed multicenter trials with a multidisciplinary team approach must be necessary to ensure accurate diagnosis and proper treatment.
Keywords: botulinum toxin therapy, oromandibular dystonia, oral dyskinesia, bruxism, functional (psychogenic) movement disorder, palatal tremor
1. Introduction
The stomatognathic system is an anatomic and functional unit composed of hard and soft tissues and has been studied in relation to occlusion and temporomandibular disorders [1,2]. The hard tissues include the bones forming the mandible and maxilla, dental arches, teeth, and temporomandibular joints, and the soft tissues include the masticatory, lingual, lip, cheek, and lower facial muscles, as well as the nervous and vascular supplies [3]. This system plays important roles in the various indispensable functions, such as chewing, swallowing, speaking, breathing, and in making facial expressions [3]. Dentists and oral surgeons specialize in the stomatognathic system and are the first healthcare professionals to see many patients with symptoms in that area. However, these professionals cannot always properly diagnose and treat involuntary movements in the stomatognathic system, as some cases require consultation with a neurologist, neurosurgeon, or psychiatrist [3,4].
Botulinum neurotoxin (BoNT) is the exotoxin of Clostridium botulinum, a Gram-positive, spore-forming bacterium. Kerner was the first to describe the symptoms of botulism in detail [5]. Van Ermengem isolated the microorganism Bacillus botulinus [6]. In 1979, Scott was the first to use BoNT therapeutically for strabismus via injection to the extraocular muscles [7]. The clinical applications of BoNT have since expanded to treat ophthalmic, neurological, gastrointestinal, urological, orthopedic, dermatological, dental, secretory, painful, cosmetic, and other diseases, and applications to the orofacial region have gained particular attention [8,9,10,11,12,13]. Target orofacial disorders include oromandibular dystonia (OMD) [14,15,16,17,18,19,20,21,22,23,24,25], hemifacial spasm [26,27], facial synkinesis [28], orolingual dyskinesia [29], functional (psychogenic) dystonia [30], trigeminal neuralgia [31,32,33,34,35,36,37], orofacial pain [38,39,40,41,42,43,44,45], temporomandibular disorder [46,47], temporomandibular joint dislocation [48,49], bruxism [50,51,52,53,54,55,56,57], palatal tremor [58,59], hypersalivation [60,61], spasmodic dysphonia [62,63], essential voice tremor [64], first bite syndrome [65,66], and Frey syndrome [67,68].
This study aimed to review the clinical problems, treatment challenges, and proposal for future studies of BoNT therapy for OMD, oral dyskinesia, bruxism, functional stomatognathic movement disorder (functional movement disorders in the stomatognathic system) [30], and palatal tremor from the perspective of an oral surgeon.
2. The Clinical Problem: History, Presentation, and Epidemiology
2.1. OMD
Dystonia is a hyperkinetic movement disorder characterized by sustained or intermittent muscle contractions that result in abnormal repetitive movements and/or postures [69]. Dystonia is categorized along two axes: (1) clinical characteristics, including the age at onset; body distribution (focal, multifocal, segmental, hemidystonia, and generalized); temporal pattern and associated features (additional movement disorders or neurological features), and (2) etiology: inherited, acquired, and secondary [69]. The term ‘dystonia’ was coined in 1911 by Oppenheim [70]. Before the concept of ‘dystonia’ was published, Romberg described various cases of masticatory muscle spasms due to a variety of pathogenesis in his textbook [71]. Among the cases, a few can be diagnosed as OMD, representing the first reports of this condition. The term ‘oromandibular dystonia’ was first introduced by Marsden in 1976 [72]. OMD is a focal type of dystonia characterized by contractions of the masticatory, lingual, pharyngeal, and/or muscles of the stomatognathic system [3,4,20,21,73,74,75,76,77,78,79,80].
2.1.1. Presentation
OMD symptoms include masticatory disturbances, biting of the tongue or cheek membrane, limited mouth opening, pain or discomfort of the muscles, dysphagia, dysarthria, esthetic problems, upper airway obstructions [19], and temporomandibular joint dislocations [49]. Most of these symptoms can impair daily activities, social embarrassment, cosmetic disfigurement, inability to work, and unemployment, forming a significant impact on the overall quality of life of the patient [3,4,78,79,80]. Based on the site and direction of abnormal dystonic movements, OMD is classified into six subtypes: jaw closing, jaw opening, lingual, jaw deviation, jaw protrusion, and lip dystonia [3,4,78,80].
Italian movement disorder experts developed diagnostic recommendations for OMD, pointing to patterned and repetitive oromandibular movements/postures—either spontaneous or triggered by motor tasks [81]. If present, a sensory trick (geste antagoniste) confirmed the diagnosis of OMD [81]. In patients who did not manifest a sensory trick, the active exclusion of clinical features related to the condition mimicking dystonia was necessary for diagnosis [81]. OMD is usually diagnosed based on the characteristic clinical features of focal dystonia and electromyography (EMG) findings [3,73,78]. Patient clinical features include stereotypy, task specificity, sensory tricks, co-contraction, and morning benefit [3,4,78,82]. Patients with OMD exhibit different stereotypical patterns of muscle contraction according to subtype. Stereotypy was observed in 95.8% of 385 patients with OMD in one study [78]. OMD symptoms often appear as only task-specific, for example, while speaking or chewing, in its early phase. Notably, 69.9% of patients with OMD showed task specificity in one study [78]. A typical example of task-specific dystonia in the oral region is embouchure dystonia, which occurs only during the performance of wind instrument players [83]. Sensory tricks are physical movements or positions that can temporarily ameliorate the symptoms of dystonia [3,4,78,82]. Such sensory tricks were observed in 51.4% of patients with OMD in one study [78]. The symptoms of dystonia tend to be milder in the morning with large inter-individual variations in their duration; this phenomenon is called ‘morning benefit’ and was reported in 47.3% of patients with OMD [78]. Another symptom, co-contraction, refers to a loss of the reciprocal inhibition of muscular activities, causing involuntary simultaneous contractions of the agonist and antagonist muscles. Jaw closing muscle contraction during mouth opening can limit the maximal mouth opening, and the occurrence of such contractions while speaking or eating can hamper speech or mastication [3,4,78,82]. The overflow phenomenon involves the activation of muscles that are unnecessary for a task, interfering with normal movement [82]. Dystonic contracture of the masticatory muscles may expand to the orbicularis oris; orbicularis oculi; or other facial, neck, and shoulder muscles [82].
Dopamine receptor-blocking agents, including antipsychotics, tricyclic antidepressants, antiemetics, and other medications for gastrointestinal disorders, can induce tardive dystonia and represent common causes of acquired dystonia [84]. Some genetic disorders (DYT-THAP1, DYT-TAF1, DYT-ATP1A3, and DYT-KMT2B) are also characterized by OMD in the clinical spectrum [84].
2.1.2. Epidemiology
The mean age of OMD onset is in the 50s [76,79,80]. Notably, women are approximately twice as frequently affected as men, indicating female predominance (2:1) [76,79,80]. OMD can occur in isolation; however, it may present together as segmental or generalized dystonia. For example, comorbid OMD and blepharospasm can form together as a segmental dystonia [85,86]. Common comorbidities of OMD include cervical dystonia, writer’s cramp, and spasmodic dysphonia [3,78,79,84]. The ratio of isolated OMD among all OMD cases differs considerably as reported by neurologists (focal, 39%; segmental, 43%; generalized, 10%) [79] and an oral surgeon (focal, 90.8%; segmental, 10.4%; multifocal, 6.3%) [80]. This discrepancy occurred because neurologists assessed several cases of OMD associated with neurological diseases, whereas the oral surgeon was able to identify numerous mild cases [80].
In a meta-analysis, Steeves et al. [87] estimated the prevalence of primary dystonia to be 16.43 per 100,000 persons, of cervical dystonia to be 4.98, of blepharospasm to be 4.24, and of OMD to be 0.52. The estimated prevalence of OMD varies from 0.1 to 6.9 per 100,000 populations [87,88,89,90,91,92,93,94,95,96]. The prevalence of OMD has been postulated to be considerably higher than previously estimated [3,78]. A recent study [80] reported the crude prevalence of OMD to be 9.8 per 100,000 persons (idiopathic dystonia, 5.7; tardive dystonia, 3.4), with an incidence of 2.0 per 100,000 person/years (idiopathic dystonia, 1.2; tardive dystonia, 0.68). The prevalence was 13.0 and 6.3 in 100,000 persons for women and men, respectively [80]. The study postulated that OMD may have an equal or even higher prevalence than cervical dystonia or blepharospasm [80]. Approximately 70% of patients with OMD visited dentists, and 60% of patients saw oral surgeons in one study [97]. However, approximately 90% of the patients had not been diagnosed correctly [97]. A vast majority of the patients had been diagnosed with temporomandibular disorders, bruxism, or psychiatric diseases [3,4,78,97]. Several patients continued the treatment of temporomandibular disorders or bruxism without effects, eventually discontinuing treatment and abandoning further consultations [3,4,78,97]. OMD is considered a rare disorder; however, in reality, the cases are simply incorrectly diagnosed.
2.2. Oral Dyskinesia
Dyskinesia is a general term for involuntary movements in which chorea, akathisia, tremor, ballism, athetosis, tic, and myoclonus occur in one or more combinations [98,99]. Historically, ‘dyskinesia’ referred to oro-buccal-lingual dyskinesia [98,99]. Subsequently, several involuntary movements were associated with this condition, and ‘dyskinesia’ became the general term for various movement disorders. This review focuses on oral dyskinesia. In the 1950s, neuroleptic medications were introduced, revolutionizing the treatment of psychiatric diseases, such as schizophrenia. Oral dyskinesias are often related to such drugs, particularly dopamine receptor-blocking agents, a category of medications that includes first- and second-generation antipsychotics [98,99]. This type of dyskinesia is called tardive dyskinesia and includes a group of delayed-onset iatrogenic movement disorders [98,99,100]. The term ‘tardive dyskinesia’ was first described in 1964 [101].
2.2.1. Presentation
Oral dyskinesias are characterized by repetitive, involuntary, uncontrollable movements, such as lip pursing, pouting, smacking, and sucking, facial grimacing, tongue licking, writhing, protrusion and laterotrusion, and chewing-like motion [98,99]. Complications related to oral dyskinesia include mucosal traumatic lesions resulting from friction or biting injuries; inability to wear dentures; difficulties in speech, chewing, and swallowing; and social embarrassment [100]. In severe cases, repeated dyskinetic movements of the lower lip can result in the penetration of the skin [82]. Levodopa remains the primary medicine for controlling motor symptoms in Parkinson’s disease; however, complications cause dyskinesia [98,99,100,102]. Hyperkinetic movements are triggered by the ON phase and occur during the OFF phase or in both phases [102].
Tardive dyskinesia develops during exposure to drugs, such as dopamine receptor-blocking agents, including antipsychotics, tricyclic antidepressants, antiemetics, and other medications administered for gastrointestinal disorders, for at least three months (or one month in patients aged ≥60 years) or within four weeks of withdrawal from an oral medication (or within eight weeks of withdrawal from a depot medication) [103]. The risk of tardive dyskinesia is reported to be three to six times greater in elderly patients than in younger populations [104,105]. Patients with drug-induced dyskinesia tend to show severe lingual dyskinesia and grimacing, with more frequent extensions to limb or trunk musculature [99]. The pathophysiology of tardive dyskinesia remains poorly understood; however, striatal dopamine D2 receptor supersensitivity has been the widely-accepted explanation [98,99]. First-generation neuroleptics with high dopamine D2 receptor occupancy are thought to carry a higher risk of tardive dyskinesia than second-generation medications with low D2 receptor occupancy, such as clozapine and quetiapine [98,99].
Oral dyskinesia may occur in relation to neurodegenerative disorders (Huntington’s disease and neuroacanthocytosis) or neuropsychiatric conditions (chronic schizophrenia, Rett syndrome, and dementia) [99]. Furthermore, it may be induced spontaneously and peripherally (edentulousness or ill-fitting prosthesis) [99].
2.2.2. Epidemiology
Dyskinesias were noted in nearly one-third of patients with schizophrenia prior to the introduction of antipsychotic medications [106]. The reviews showed that the prevalence of dyskinesia in patients with schizophrenia who had not been treated with antipsychotic drugs was 4.2% [107], 5% [108], or 12% [109]. The estimated rate of tardive dyskinesia in patients with schizophrenia who had been treated with antipsychotic medications was 15–20% [107,110] or 20–50%, with the prevalence increasing with advanced age [103]. The largest review conducted, involving 34,555 patients, reported an average prevalence of 20% [108].
Edentulousness has been thought to be a common cause of oral dyskinesia [99,111]. One study compared 75 edentulous participants (mean age: 62 years) seen in a dental clinic to 75 age-matched controls with natural teeth [111]. Overall, 12 (16%) of the edentulous participants showed oral dyskinesia, 9 exhibited mild dyskinesia, and 3 showed marked stereotypic dyskinesia. Six (50%) of the edentulous participants with oral dyskinesia had no dentures, and one participant wore ill-fitting dentures.
In one study, 38 (3.7%) out of 1018 participants aged ≥60 years attending a daycare center were found to have oral dyskinesia without apparent cause [112]. The over-all prevalence was estimated to be 3.7% (4.1% for women and 2.9% for men) [112]. Participants with dyskinesia due to undefined causes reported more frequent ill-fitting prosthetics, oral pain, and a lower rate of perception of good oral health than those without oral dyskinesia [112]. In a survey of 352 edentulous elderly individuals, 7% displayed oral stereotypes, 4% reported tardive dyskinesia, and 2% exhibited antidepressant drug-related dyskinesia; furthermore, ill-fitting dentures were suggested as a possible triggering factor for the majority of patients [112]. Spontaneous oral dyskinesia is thought to be comparatively infrequent in the elderly population compared to rates in populations receiving antipsychotic drugs [99,107].
The prevalence of dyskinesia in untreated patients with chronic schizophrenia was estimated to be 12% in one review [108]. In another study [113], never-medicated patients with chronic schizophrenia were reexamined at 18 months, and a prevalence of dyskinesia 57% was reported. In other studies, prevalence ranged from 1.5% [114] to 31.7% [115]. The prevalence estimates of spontaneous orofacial dyskinesia in healthy elderly individuals show significant variations depending on the individuals evaluated, as with dystonia [87,88,89,90,91,92,93,94,95,96].
2.3. Bruxism
The term bruxism is derived from the Greek word ‘brychei’, which means to grind or gnash the teeth [116]. Bruxism is classified into sleep and awake bruxism, which are defined as masticatory muscle activities that occur during sleep and wakefulness, respectively [117]. Sleep bruxism is characterized as rhythmic or nonrhythmic, and awake bruxism is characterized by repetitive or sustained tooth contact and/or by bracing or thrusting of the mandible [117].
2.3.1. Presentation
Although the etiology of bruxism has not yet been fully elucidated, a multifactorial etiology was postulated, including biological; psychological (anxiety and stress); and exogenous (consumption of some drugs, caffeine, tobacco, and/or alcohol) causes [117,118,119]. Bruxism has been recognized to be related to tooth wear or destruction; failure of dental prostheses or implants; pain in the teeth, masticatory muscles, or temporomandibular joints; temporomandibular disorders; masseter muscle hypertrophy; or tension headache [117,118].
2.3.2. Epidemiology
Bruxism is a very common condition, observed to some degree during the lifetime of approximately 85–90% of the general population [120]. In many of these cases, the symptoms are temporary, the patients themselves are unaware of the symptoms, and active treatment is not required [117,118]. In earlier studies, the estimated prevalence of sleep bruxism awareness was based on reports by parents or sleep partners [121]. Recently, polysomnography with audio–video recording or ambulatory EMG devices have been used for a definite diagnosis [121]. Thymi et al. [121] suggested that, in future studies using ambulatory EMG instruments, the focus may require to shift to the concept of scoring the whole spectrum of masticatory muscle activity.
A prevalence of 5.0% was found for awake bruxism and 16.5% for sleep bruxism [122]. A recent umbrella review reported that the prevalence of awake bruxism was 22–30% and that of sleep bruxism was 1–15%; sleep bruxism among children and adolescents was 3–49% [118]. Gender differences with respect to sleep bruxism are not obvious, as most studies reported an equal prevalence in men and women [123].
2.4. Functional Movement Disorder
Functional movement disorders are part of a spectrum of functional neurological disorders and are among the most common causes of neurological disability [124]. Recently, the term ‘functional’ has been used more frequently than ‘psychogenic’ [125]. These disorders are thought to be caused by a complex interplay of biopsychosocial vulnerabilities under exposure to psychosocial and/or physical triggers [126]. Charcot [127] first described the functional facial movement disorder as ‘l’hémispasme glosso-labié hystérique’. Although functional movement disorders often have characteristic clinical features in the orofacial region, their diagnosis is challenging [128]. Diagnoses of such conditions should rely not on the exclusion of organic diseases or the presence of psychological symptoms but on the observation of specific clinical features [126,129,130,131]. The misdiagnosis of OMD as a temporomandibular disorder or a psychogenic disease is frequent. Nevertheless, the situation in functional movement disorders in the stomatognathic system is more serious [30]. Thus, functional movement disorders in this region are under-recognized [30].
2.4.1. Presentation
Despite the absence of specific electrophysiologic tests or a gold standard for diagnosis, functional movement disorders are diagnosed with clinically definite certainty based on the available criteria, regardless of any psychiatric symptoms [130,131]. Functional movement disorders often have characteristic clinical features in the orofacial region, including tonic muscular spasms, involving the lip, eyelids, perinasal region, and forehead [127,132,133,134]. The most common phenotype is tonic mandibular deviation accompanying ipsilateral downward and lateral lip pulling, seen in 84.3% of patients with facial functional movement disorders involving the craniofacial region [128]. Uni- or bilateral orbicularis oculi and platysma contraction are often associated [128].
In a previous study [30], 10-item inclusion criteria were formulated based on previously reported criteria for functional movement disorders [126,129,130,131] or clinical features in facial functional dystonia [128,132,133,134] to comprehensively assess 58 patients with functional movement disorders in the stomatognathic system. The criteria included 10 symptoms, and the prevalence of each was as follows: rapid onset, 74.1%; static course, 60.3%; paroxysmal symptoms, 86.2%; spreading to multiple sites, 89.7%; spontaneous remission, 58.6%; inconsistent symptoms, 93.1%; distractibility, 67.2%; incongruous symptoms, 91.4%; lack of sensory tricks, 81.0%; and suggestibility, 63.8% [30]. A functional dystonia phenotype (unilateral lower lip pulling and jaw deviation) was observed in 44.8% of the patients. The characteristic and distinguishable features of functional stomatognathic movement disorders included rapidly repeating lateral or tapping mandibular and tongue movements (27.6%), which considerably fluctuated with respect to the speed and direction [30].
The most prevalent complaint was pain (50%) in one study [30], while another study reported that 24.6% of patients complained of painful spasms [128]. Dysarthria (27.6%) and masticatory disturbances (15.5%) were also more common in this study than in previous reports [128,133]. This likely occurred because the study exclusively evaluated patients with symptoms in the stomatognathic region [30]. Depression was observed in 38% of patients with functional movement disorders in a previous study [128] and in 39.7% of patients in another study [30]. Frequent precipitating events included dental treatment (44.8%) and physical trauma (12.1%) [30].
2.4.2. Epidemiology
Tremor, dystonia, myoclonus, and gait disturbance are the most prevalent presentations of functional movement disorders [126,129,130,131]. Such symptoms were seen in 5–20% of patients in a movement disorder clinic, functional dystonia being one of the most common [135]. Functional neurological disorders have an estimated prevalence of 50 per 100,000 population based on a community registry [124]. Involvement of the face represented 16.3% of all functional movement disorders in a large study [128]. Functional movement disorders of the orofacial region are prevalent in women (91.8% [128] and 72.4% [30]). The mean age at onset was 37 years [128] and 46.2 years [30].
Only one study has described functional movement disorders in the stomatognathic system [30]. In this work, 58 patients were diagnosed with functional stomatognathic movement disorders out of 1720 patients with complaints of involuntary movements or contracture of the masticatory, lingual, and/or lower facial muscles [30]. Therefore, the prevalence of this condition may be very low.
2.5. Palatal Tremor
Palatal tremors, which cause clicking tinnitus, were first documented by Boeck [136]. Two types of palatal tremor (also called palatal myoclonus) are described in the literature: essential and symptomatic palatal tremor [137,138]. Essential palatal tremor reveals no underlying structural pathology, whereas symptomatic palatal tremor occurs due to any lesion within the dentato–rubral–olivary pathway [139,140]. Essential palatal tremor occurs due to contraction of the tensor veli palatini muscle, supplied by the fifth cranial nerve, and symptomatic palatal tremor is due to the contraction of the levator veli palatini muscle, supplied by the ninth and tenth cranial nerves [141]. This review focuses on essential palatal tremors.
2.5.1. Presentation
Palatal tremors are involuntary contractions of the soft palate often accompanied by a clicking sound [59,142]. Palatal tremor is usually attributed to a dysfunction or lesion in the Guillain-Mollaret triangle; however, many other causes exist, including functional (psychogenic) factors [143]. Symptoms include clicking tinnitus, nonaudible awareness of palatal movements, and rhinolalia [59]. The most troublesome symptom for the patient is synchronous audible clicking tinnitus (ear clicking) accompanying the abnormal movements [59]. An essential palatal tremor is much more likely to present with a clicking tinnitus than a symptomatic tremor [59]. Clicking tinnitus is produced by contractions of the tensor veli palatini muscle, which opens the Eustachian tube, causing a sudden drop in surface tension within the tube [138,140].
2.5.2. Epidemiology
Zadikoff et al. [140] reviewed the existing literature on essential palatal tremor and found a male:female ratio of 1:1. Sinclair et al. [59] reported that patients were more commonly female (60% vs. 40%). Deuschl et al. [138] reported the persistence of essential palatal tremor during sleep in 50% of patients. The mean age at symptom onset was 35.6 years, including childhood onset. The essential palatal tremor began after a viral respiratory infection in 40% of patients [59]. The frequency of essential palatal tremor is not only highly variable among different patients; however, it can also vary within a single individual [139].
3. Treatment Challenges and Pitfalls
3.1. OMD
OMD can be part of the clinical spectrum of various neurological diseases, including Parkinson’s disease, pantothenate kinase associated neurodegeneration, Wilson’s disease, chorea-acanthocytosis, Lesch Nyhan syndrome, and Leigh syndrome, or of ischemic or hemorrhagic stroke, tumors, infarction, and brain injury [84]. If such diseases have already been diagnosed and treated, OMD must be addressed simultaneously by the attending physicians [3,4]. However, if not diagnosed yet, the patient should be referred to specialists [3,4]. Likewise, collaboration with a psychiatrist is required for the treatment of tardive dystonia.
The treatment of OMD must be multimodal and highly individualized, and the methods include pharmacological [4,82,84], BoNT [14,15,16,17,18,19,20,21,22,23,24,25,75,144,145,146,147,148,149,150,151,152,153,154,155], muscle afferent block [73,156,157], occlusal splint [158,159], and surgical therapies (coronoidotomy) [160,161,162]. Due to the number of muscle spindles, muscle afferent block therapy is more effective for jaw closing muscles than for jaw opening muscles [73,156]. A sensory trick splint is particularly successful in patients with muscle hyperactivity of the jaw closing muscles. In one study, 83.7% of the responders with splints presented with jaw closing dystonia [158]. Patients who showed improvement with the use of splints and continued to wear them for at least three months were defined as responders [158], while patients who showed little or no effect and/or were unable to insert splints were defined as non-responders [158]. Intraoral sensory tricks were significantly more common in responders (60.2%) than in non-responders (13.3%) [158]. Coronoidotomy is only indicated for severe jaw closing dystonia [160,161]. However, one-third of the operated patients required additional BoNT injections into the masseter and/or medial pterygoid muscles [161]. This review will focus on BoNT therapy.
Chemodenervation with BoNT is considered the first line of treatment for OMD. Currently, four FDA-approved and commercially available BoNT formulations. The three types of botulinum toxin type A available are onabotulinumtoxinA (Botox; Allergan, Irvine, CA, USA), abobotulinumtoxinA (Dysport; Ipsen-Pharma, Berkshire, UK), and incobotulinumtoxinA (Xeomin; Merz Pharma, Frankfurt am Main, Germany); rimabotulinumtoxinB (Myobloc in the USA; Supernus Pharmaceuticals, Inc, Rockville, MD; and Neurobloc in Europe, Sloan Pharma, Baar, Switzerland) is a botulinum toxin type B preparation [13,163,164]. The following ratios are often used in clinical practice: onabotulinumtoxinA:incobotulinumtoxinA = 1:1; onabotulinumtoxinA: abobotulinumtoxinA = 1:2.5, and onabotulinumtoxinA:rimabotulinumtoxinB = 1:50 [13,164]. Although BoNT is frequently used in major countries for treatment, it has not been officially approved for OMD.
For the first injection, the dose of BoNT must be low because effects vary between individuals [4]. In the subsequent injections, the dose should be adjusted individually corresponding to the effects to reduce the risk of side effects or antibody development and minimize the cost. A risk of developing neutralizing antibodies exists with the long-term use of BoNT [13,165]. The factors that increase the risk of developing resistance to include a high protein load in some formulations, large individual and cumulative doses, and short intervals [165,166,167,168]. Since the dose for OMD is relatively small, the risk of antibody development is low; however, a case was reported of antibody development after a large amount of BoNT was injected intensively [15]. The contraindications of BoNT include systemic neuromuscular junction disorders (myasthenia gravis, Lambert-Eaton syndrome, and amyotrophic lateral sclerosis); current or possible pregnancy; and lactation.
To predict the efficacy of injected BoNT, 3–5 mL of 0.5% lidocaine was injected into the hyperactive muscles of patients in one study, and involuntary movements were carefully observed [45]. If the patients showed changes at all, BoNT was considered not likely to be effective. If the patients showed an improvement of symptoms under the effects of the local anesthetic, subsequent appointments for BoNT injections were recommended [45].
A complete understanding of the local anatomy of the stomatognathic system is a prerequisite for target muscle selection and safe injection without complications [4,20,25]. BoNT is reconstituted with normal saline to reach a final concentration of 2.5–5 units/0.1 mL. Differences in the concentration may affect diffusion; however, no difference in effect was seen in a study for blepharospasm [169]. A disposable hypodermic needle electrode (37 mm × 25 G, 50 mm × 25 G) is used for injection into the target muscles, and accurate placement of the electrode is verified by evaluating EMG activity [4,20,25]. Subsequently, after aspiration, the necessary units of botulinum toxin are injected into the target muscles.
Sonography is important for identifying target muscles and preventing damage to other tissues and is often used for cervical dystonia [170,171]. This method is also very useful for OMD and is recommended for use in combination with other methods such as EMG.
The maximum bite force is measured bilaterally on the molars three times using an occlusal force meter [4,45,172]. The muscles and doses of BoNT are then individually determined for each patient based on their symptoms and occlusal force [4,45,78,172]. The injection is continued until the patient is satisfied with the effect [4,45]. The injection interval is three to six months, depending on patient symptoms [4,45,172].
3.1.1. Jaw Closing Dystonia
Jaw closing dystonia was observed in 59.5% of patients with OMD [78]. In severe cases, the patients cannot open the mouth at all because of the involuntary contraction of the bilateral temporalis and masseter muscles [160,161]. The recommended target muscles and doses of BoNT for jaw closing dystonia [4,45,173] are summarized in Table 1.
![Table 1: Recommended target muscles and doses of BoNT (onabotulinumtoxinA: Botox®) for jaw closing dystonia [4,45,173].](https://static.wixstatic.com/media/ab0f77_d17eee22628241bdb2f52bb06547fa75~mv2.jpg/v1/fill/w_980,h_454,al_c,q_85,usm_0.66_1.00_0.01,enc_auto/ab0f77_d17eee22628241bdb2f52bb06547fa75~mv2.jpg)
Recommended target muscles and doses of BoNT (onabotulinumtoxinA: Botox®) for jaw closing dystonia [4,45,173].
Masticatory disturbance may be a side effect of an excessive loss of occlusal force. The maximum occlusal force should be measured before and after treatment with BoNT to prevent an excessive loss of chewing force [4,172].
Masseter Muscle
The main target muscle of BoNT treatment for jaw closing dystonia is the masseter muscle, which comprises a superficial and a deep part [4,173]. Posteriorly, the muscle is covered by the parotid gland, and care must be taken not to damage it with a needle [4,173]. An ultrasound-guided injection makes it possible to distinguish the masseter muscle from the parotid gland [4,173]. BoNT is injected 10–15 mm into the most prominent region during jaw clenching, with 10–50 units (depending on the condition) at three points (Figure 1) [4,173].
![Figure 1: Injection sites for the masseter and temporalis muscles [4,45,173].](https://static.wixstatic.com/media/ab0f77_289e42e602a944a791cc6c00bcc5ea8e~mv2.jpg/v1/fill/w_664,h_734,al_c,q_85,enc_auto/ab0f77_289e42e602a944a791cc6c00bcc5ea8e~mv2.jpg)
Temporalis Muscle
After careful examination including EMG, occlusal force and palpation, BoNT is often injected into the temporalis muscle at the same time. This muscle, particularly anterior fibers, elevates the mandible, and pulls it back with posterior fibers. Notably, 10–50 units of BoNT are injected 10–15 mm deep at three sites (Figure 1) [4,173].
Medial Pterygoid Muscle
Repeated injections into the masseter and temporalis muscles can cause tension on the medial pterygoid muscle due to the ‘whack-a-mole phenomenon’ [161,174]. This phenomenon can be explained as follows: When a dystonic muscle has been improved by BoNT treatment, one of the other muscles with the same function becomes more active [161,174]. Subsequently, when BoNT is injected into the latter muscle, another muscle with a similar function gradually becomes dystonic [161,174]. It is therefore necessary to inject BoNT into the medial (internal) pterygoid muscle. The medial pterygoid muscle is accessible via intraoral and extraoral approaches (Figure 2). With the intraoral method, the patient must gargle with a mouthwash solution; then, the needle should be positioned at an angle of 20° to the rear and upward and then to the side by 20° after palpation of the muscle in relation to the occlusal plane (Figure 2) [173]. The needle should be inserted up to a depth of 15–20 mm. BoNT is injected in 10–30 units. The correct placement of the needle in the target muscle should be monitored by EMG [161,173,174]. For the extraoral method, the patient’s head should be tilted towards the contralateral side. The needle is then inserted into the submandibular skin, 10 mm forward from the angle of the lower jaw, parallel to the inner side of the mandible, and at a depth of 15–20 mm (Figure 2) [161,173,174].
Injection methods for the medial pterygoid muscle; intraoral approach (blue arrow) and extraoral oral approach (red arrow) [4,22,49,173,174].
Patients who mainly exhibit grinding also often report severe tenderness in the lateral pterygoid muscle. The details of this muscle are described in Section 3.1.2.
3.1.2. Jaw Opening, Deviation, and Protrusion Dystonia
The occurrence rates of jaw opening, jaw deviation, and jaw protrusion dystonia in patients with OMD are 12.7%, 5.5%, and 3.1%, respectively [78]. In jaw opening and protrusion dystonia, the bilateral lateral pterygoid muscles show involuntary hyperactivity [22,173,174]. In contrast, in jaw deviation dystonia, the muscle on the contralateral side of the deviation exhibits abnormal contractions [22,173,174]. In the most severe cases, the temporomandibular joint is dislocated [19,49]. The recommended target muscles and doses of BoNT for jaw opening, jaw deviation, and jaw protrusion dystonia [4,22,49,173,174] are summarized in Table 2.
Recommended muscles and doses of BoNT (onabotulinumtoxinA: Botox®) for jaw opening, deviation, and protrusion dystonia [4,22,49,173,174].
Lateral Pterygoid Muscle
The lateral (external) pterygoid muscle is a two-headed muscle comprising a superior (upper) and an inferior (lower) head [22,173,174]. As the bilateral inferior heads contract, the condyle is pulled forward and slightly downward. If the muscle is only activated on one side, the inferior jaw rotates around a vertical axis that runs through the contralateral condyle, and it is pulled medially to the contralateral side [22,173,174]. The superior and inferior heads are activated alternately during chewing, such that the inferior head contracts during mouth opening while the superior head relaxes. Upon closing of the mouth, the actions are reversed. [22,173,174,175,176].
The maxillary artery arises behind the neck of the mandible and is initially embedded in the parotid gland [22,173,174]. Known anatomical differences exist between Japanese and Caucasian populations in the course of the maxillary artery in relation to the lateral pterygoid muscle [22,173,174]. In 92.7% of Japanese individuals, the maxillary artery runs laterally to the lower head [22,173,174]. However, in Caucasians, the artery more often runs medially to the muscle (38%) [22,173,174]. Injury to the maxillary artery during needle insertion can result in arterial bleeding, swelling, and bruising. Both intraoral and extraoral methods are available for BoNT injection; when injecting into the lateral pterygoid muscle, medical practitioners must be aware of these anatomical differences (Figure 3) [22,173,174].
Injection methods for the lateral pterygoid muscle: intraoral approach (blue arrow) and extraoral oral approach (red arrow) [4,22,49,173,174].
The extraoral injection is easy to administer; however, BoNT can only be injected in a limited area [22,173,174]. Further, a risk of mouth dryness exists [147]. In contrast, the intraoral injection can be applied directly into the region with muscle tension with EMG monitoring. With the intraoral method, the needle is inserted 20–30 mm into the inferior head of the mucobuccal fold next to the upper second molar [22,173,174]. The angle of needle insertion is 30° upwards against the occlusal surface and 20° inwards against the sagittal plane (Figure 3). BoNT is injected in 10–50 units, depending on the condition. With the extraoral method, after palpating the infratemporal fossa, the needle can be inserted perpendicular to the skin 20–30 mm deep through the notch in the mandible (Figure 3) [22,173,174].
Computer-aided design and manufacturing process was used to develop a needle guide to reliably administer BoNT into the inferior head of the lateral pterygoid muscle [22,173,174]. Computed tomography and scan data of the upper jaw model are transferred to a computer, and the two most suitable points on the lower head are determined [22]. The needle guide is subsequently mounted in the oral cavity, and the needle is inserted to the planned depth. The experiments showed that the needle was easily inserted without any complications in all the procedures [22].
Digastric Muscle
The digastric muscle comprises two muscle bellies (anterior and posterior) connected by an intermediate tendon [4]. The anterior belly of the digastric muscle acts in the early phase of opening the mouth by lowering the chin [175,176]. Injection into the anterior belly can cause dysphagia and should be carefully monitored. BoNT is injected in 5–10 units [4]. Patients with OMD or bruxism have often reported tenderness in the posterior belly of the digastric muscle. If the patients have tenderness in the muscle, the muscle can be easily palpable. Since blood vessels and nerves run nearby, approximately 2.5–5 units of BoNT should be carefully injected under EMG guidance [4].
Temporalis Muscle and Platysma
If the effect of BoNT injections not satisfactory for patients with jaw deviation dystonia, BoNT (10–20 units) should be injected into the posterior fiber of the ipsilateral temporalis muscle. In some patients with jaw opening dystonia, the platysma may become hyperactive and require injection (10–20 units).
3.1.3. Lingual Dystonia
Lingual (tongue) dystonia is characterized by involuntary, often task-specific contractions of the tongue muscle [177]. Lingual dystonia was found in 25.5% of patients with OMD [78]. Lingual dystonia is divided into four subtypes: protrusion, retraction, laterotrusion, and curling [25].
The tongue comprises four extrinsic (genioglossus, hyoglossus, styloglossus, and palatoglossus muscles) and four intrinsic (superior longitudinal, inferior longitudinal, transverse, and vertical muscles) muscles [25,178]. The extrinsic muscles control tongue position, while the intrinsic muscles control movement [25,178]. Although serious complications of BoNT injection, including life-threatening dysphagia, aspiration pneumonia, and breathing difficulties, were reported in previous studies [179,180], the therapy has been recognized as a promising option in recent years [25,181,182].
The subjective improvement after the injection of BoNT was 77.6% in 136 patients with lingual dystonia [25]. The greatest improvement was seen for curling type dystonia (81.9%), whereas the retraction type exhibited the lowest improvement rate (67.9%) [25]. Mild dysphagia occurred in 12.5% of the patients; however, this resolved spontaneously within a few days to two weeks. No serious side effects were observed [25]. Lingual dystonia is often accompanied by jaw opening dystonia. For such patients, injection into the lateral pterygoid muscle is necessary [4]. The recommended target muscles and doses of BoNT for lingual dystonia [4,25,173] are summarized in Table 3.
Genioglossus and Other Tongue Muscles
The genioglossus muscle is the dominant muscle for tongue protrusion [178]. BoNT injection into the lingual muscle occasionally causes life-threatening complications, such as serious dysphagia [179], aspiration pneumonia [179], and swallowing or breathing difficulties [180]. Investigators have reported various methods for BoNT injection, primarily the submandibular approach [25,179,180,181,182,183,184,185], with intraoral approaches also reported [186]. In the submandibular method, injection is performed in one or two sites bilaterally.
A more detailed injection method for the four subtypes of lingual dystonia has been described, depending on the direction of the tongue deviation [25,173]. The dose of BoNT therapy should be started at 10–20 units and gradually increase to 40–50 units, corresponding to patient symptoms [25,173]. The appropriate doses of BoNT (15–60 units) is then determined based on EMG examination and patient symptoms (Table 3).
For protrusion type dystonia, approximately 50–100% of the total doses are injected into the bilateral genioglossus percutaneously through the submandibular region. The insertion points are defined as two sites 25–30 mm posterior from the midline of the body of the mandible and 15–20 mm apart from each other (Figure 4A) [25]. If tongue protrusion occurs while simultaneously curling up or down, the remaining doses are injected into the superior longitudinal muscle (5 mm depth; injection to counteract tongue protrusion) or into the inferior longitudinal muscle (10–15 mm depth; injection to counteract curling) [25]. If laterotrusion occurs with protrusion, BoNT is administered into the superior and inferior longitudinal muscles on the deviated side (Figure 4B) [25]. If the tongue shows flattening or narrowing, the remaining BoNT is injected into the bilateral vertical muscle (10 mm in depth; to counteract protrusion) and the bilateral transverse muscle (10 mm in depth; to counteract curling) [25].
Submandibular sites of BoNT injection for lingual dystonia (A). Intraoral sites for BoNT injection (B) for protrusion type (➊–➍), laterotrusion type (right deviation (➊, ➌), left deviation (➋, ➍)), ...
For retraction type dystonia, target muscles are identified after careful EMG examination. These include a wide range of tongue muscles that may undergo contraction, such as the genioglossus, intrinsic muscles, geniohyoid, and hyoglossus [25]. Appropriate doses of BoNT are in the range of 15–50 units (Table 3).
For laterotrusion type dystonia, the appropriate dose of BoNT is between 10 and 40 units (Table 3). BoNT is injected into the superior (5 mm in depth) and inferior (10–15 mm in depth) longitudinal muscles on the deviated side (Figure 4B) [25]. The inferior longitudinal muscle is more accessible from the inferior aspect of the tongue (5 mm in depth) than from the dorsum. If the genioglossus on the opposite side exhibits EMG activity, an additional injection is administered [25].
For curling type dystonia, the appropriate dose of BoNT is between 10 and 40 units (Table 3). The toxin is injected bilaterally at two or three sites from the dorsum of the tongue, approximately 5 mm in depth, into the superior longitudinal muscle (Figure 4B) [25]. BoNT is injected into the superior longitudinal muscle near the apex if curling up of the apex occurs (Figure 4B).
3.1.4. Lip Dystonia
Lip dystonia was observed in 3.6% of the reported OMD cases [78]. The orbicularis oris muscle is a sphincter that surrounds the oral orifice. According to the symptoms, BoNT should be injected into the orbicularis oris, risorius, depressor anguli oris, depressor labii inferioris, mentalis, and platysma. Since the fibers of the orbicularis oris muscle close to the orifice are responsible for pursing the lips, and the fibers distant from the orifice press the lips against the teeth [149], the dose and site should be adjusted according to the symptoms [4]. The dose of BoNT should be low (2.5–5 units) because of risk of the labial incompetence and asymmetric smile.
Lip dystonia, especially unilateral traction, can occur with functional involuntary movements [30]. Functional movement disorders often show distinguishable clinical features in the orofacial area. Treatment with BoNT is effective in some cases, but complete treatment often requires psychotherapy or physiotherapy [30].
3.1.5. Pitfalls
The largest clinical pitfall of OMD treatment seems to be a misdiagnosis. Most patients with OMD see a dentist or oral surgeon and are diagnosed with bruxism, temporomandibular disorders, and/or psychiatric disorders [78,97]. OMD is considered a blind spot between medical science and dentistry [78]. Neurologists may diagnose temporomandibular disorder as OMD, (i.e., bruxism as jaw closing dystonia and anterior disc displacement without reduction as jaw deviation dystonia) [78]. The knowledge and experience of both neurology and dental medicine are needed for proper diagnosis of OMD from temporomandibular disorders, but these two perspectives are nearly impossible to obtain simultaneously. Therefore, a simple diagnostic tool was developed to enable primary care physicians, neurologists, dentists, and oral surgeons to differentiate OMD from temporomandibular disorder and to initiate appropriate treatments rapidly [78].
A subsequent pitfall of BoNT treatment is the method of injection into the masticatory muscles. Dressler et al. [155] described in their consensus guidelines, “The Mm. pterygoidei can easily be injected through the incisura mandibulae. EMG requiring thick combination needles seems unnecessary as dystonic involvement is usually affecting both, the lateral and the medial pterygoid muscles.” Nevertheless, it is risky to inject BoNT into the lateral and medial pterygoid muscles without EMG guidance [22,173,174]. The lateral pterygoid muscle should be injected in jaw opening dystonia [22,173,174]. In contrast, the medial pterygoid muscle should be injected for patients with jaw closing dystonia [21,74,147,173]. If BoNT is erroneously injected into the lateral pterygoid muscle for jaw closing dystonia, or into the medial pterygoid muscle for jaw opening dystonia, adverse effects are expected. Since the needle is inserted at the notch by percutaneous lateral pterygoid muscle injection, penetrating the parotid gland, mouth dryness may occur due to the spread of BoNT [147]. Most OMD specialists recommend an intraoral approach [20,21,22,49,74,147].
In a systematic review [77] involving 387 patients with OMD treated with BoNT, 27.1% of the patients had side effects, most frequently dysphagia. Previously reported adverse effects of BoNT/A include temporary regional weakness, tenderness over the injection sites, minor discomfort during chewing, asymmetric smile, loss of smile, lip numbness, muscle atrophy, paresthesia, difficulty in swallowing, mouth dryness, speech changes, nasal speech, headache, hematoma, nasal regurgitation, swelling, bruising, facial asymmetry, transient edema, itching, and pain at the injection area [15,16,18,21,139,147,150,187]. Most of these effects were observed to be transient and spontaneously disappeared. Moreover, the majority of these side effects are thought to be related to the injection technique and avoided by accurate knowledge of the local anatomy of muscles, nerves, and other tissues and accurate injection procedures. The more accurately BoNT is administered into the target muscles, the more likely the improvement in patient symptoms, and the lower the risk of complications [22,25,45,49]. Empirical differences in injection techniques may be associated with adverse effects [45]. Selected dose should be as high as necessary but as low as possible.
Several authors have reported changes in the mandibular bone after BoNT injections [188,189]. In contrast, a retrospective study in adult women with masseter hypertrophy found no significant change in whole mandible volume or in cortical thickness of the mandibular ramus three months after BoNT therapy in the masseter muscles [190]. Changes in bone after BoNT therefore may not be an adverse effect but a normal physiological response related to the corrected occlusal force [45]. Injection with BoNT improves the excessive tension of the jaw elevator muscles and allows the hypertrophied muscles and bones to return to their original shape [45].
Since the symptoms of OMD can vary from patient to patient, it is difficult to objectively measure disease severity and changes after treatment [3]. In 2002, 44 patients with OMD were evaluated before and after muscle afferent block therapy using a simple clinical scoring system according to subscores for pain, mastication, speech, and discomfort [156]. In 2010, Merz et al. [191] developed and validated the Oromandibular Dystonia Questionnaire. Recently, a comprehensive measurement tool for OMD, the ‘Oromandibular Dystonia Rating Scale’ was developed and validated [3]. The scale can be useful for the comprehensive evaluation of severity, disability, psychosocial functioning, and impact on the quality of life, as well as therapeutic changes in patients with OMD [3].
3.2. Oral Dyskinesia
Preventing tardive dyskinesia during psychiatric drug administration is paramount, and the strict selection of patients to be treated with dopamine receptor-blocking agents is a prudent medical practice [98,99]. In patients receiving dopamine receptor-blocking agents, if discontinuation is possible, the drug may be delayed by slowly reducing the dose over several months [98]. Tardive dyskinesia symptoms are often alleviated but can persist indefinitely after drug withdrawal. The younger the age or the shorter the administration period, the higher the remission rate. However, a drug having a dopamine-depleting effect should be used if the medication cannot be discontinued.
Switching from a first-generation to a second-generation antipsychotic with lower D2 affinity, such as clozapine or quetiapine, may be efficacious in reducing tardive dyskinesia symptoms [98,99,192]. Chemodenervation with BoNT injections into the masticatory or lingual muscles causing dyskinesia has also been successfully applied [29]. BoNT should be injected into jaw closing, jaw opening, or tongue muscles or into muscles around the mouth (orbicularis oris, risorius, zygomatic, and mentalis muscles), according to the methods described in Section 3.1.1, Section 3.1.2 and Section 3.1.3. If the symptoms are severe and all drug therapies are found to be ineffective, deep brain stimulation, such as globus pallidus stimulation, may be performed [98]. However, there is limited evidence for the use of globus pallidus interna deep brain stimulation.
In addition, anticholinergic drugs may be used to treat idiopathic oral dyskinesia and rabbit syndrome [99]. However, the symptoms of patients with oral dyskinesia often worsen with anticholinergics. Further, elderly patients require careful monitoring of symptoms, such as dementia and constipation caused by the anticholinergic effect of this drug [99].
If orolingual dyskinesia causes the tongue or lips to come into contact with the teeth and form ulcers [82], and other therapies are ineffective, a protective guard, such as a splint, is inserted as a dental symptomatic treatment, or occasionally, the causative tooth is extracted. Furthermore, chronic undesired peripheral sensory inputs in the stomatognathic system caused by ill-fitting dentures and edentulousness, are thought to induce dyskinesia [99]. In edentulous patients with oral dyskinesia inserting dentures, adequate adjustment or relining of the dentures has successfully improved the intensity of the symptoms [193,194].
Pitfalls
Neurological, psychiatric, and dental factors may contribute, to a variable extent, to oral dyskinesia [99]. A multidisciplinary evaluation with a neurologist, psychiatrist, and dentist or oral surgeon is recommended for patient management.
3.3. Bruxism
Bruxism should not be recognized as a disorder in otherwise healthy individuals but rather as a behavior that can be a risk (and/or protective) factor for certain clinical consequences [117]. Treatments for bruxism include medication, occlusal splint, physical therapy, and cognitive behavioral therapy [118]. In recent years, BoNT therapy has been clinically applied [50,51,52,53,54,55,56,57]. Most patients with bruxism experience symptom relief via traditional methods, such as oral medications and splints. BoNT therapy should be considered in severe cases when other treatments are ineffective [172]. Prolonged, severe, and/or intense bruxism can cause the develops excessive tendonous tissue at the anterior margin of the masseter muscle, resulting in masticatory muscle tendon-aponeurosis hyperplasia and severe trismus [161,162]. In such cases, coronoidotomy is required [160,161,162].
The masseter muscle contributes to approximately 43% of the intrinsic strength of the jaw elevator muscles, to approximately 36% of the strength of the temporalis muscle, and approximately 21% of the strength of the medial pterygoid muscle [195]. Palpation, EMG, and occlusal force measurement are used to determine the target muscles [4,45,172]. In most cases, the masseter and temporalis muscles are injected first. In cases of medial pterygoid muscle tenderness, continuous injections into the masseter and temporalis muscles are administered, and if the effect diminishes, the medial pterygoid muscle is treated [4,172,173,174]. In cases with severe grinding, the lateral pterygoid muscle is often sensitive, and the lateral pterygoid muscle is also injected [4,172,173,174]. The occlusal force must be measured before and after each BoNT injection, as long-term repeated injections can result in the drop of occlusal force and masticatory disturbance [45,172].
In one study, 108 patients (33 men, 75 women) with involuntary contractions of the masseter, temporalis, and medial pterygoid muscles were treated for a total of 342 injections of BoNT [172]. The patients were refractory to oral medications, splints, myomonitor, and other treatments. After BoNT injection, the involuntary muscle tone and related myalgia were alleviated, and the maximum occlusal force between the maxillary and mandibular first molars was significantly reduced on the left (410.9 N→291.3 N) and the right (433.5 N→313.8 N) sides [172]. The average subjective improvement (self-evaluation where 0% no effect and 100% complete cure) was 82% [172]. Ahn et al. [196] studied seven patients with masseteric hypertrophy. Twenty-five units of BoNT was injected into each masseter muscle, and the differences in maximum occlusal force between the pre-injection and 2-, 4-, and 8-week post-injection values were statistically significant. However, no significant difference was seen between the values at baseline and after 12 weeks. Although the maximum occlusal force significantly decreased after injection of BoNT for the treatment of masseter hypertrophy, force gradually recovered by 12 weeks [196].
BoNT therapy is important in severe cases of bruxism, but a surgical procedure under general anesthesia should be considered in persistent, severe cases where mouth opening is completely impossible due to forceful clenching [160,161].
Pitfalls
A significant number of patients diagnosed with awake bruxism may exhibit jaw closing dystonia [3,78]. The treatment of bruxism in patients with jaw closing dystonia has a limited effect, and the differential diagnosis between awake bruxism and jaw closing dystonia is important [78]. Notably, several dental professionals are interested in and studying bruxism but not OMD. Therefore, raising awareness of OMD among dentists and oral surgeons, who are likely to see patients with OMD first, is critical.
Adverse reactions from BoNT injections are uncommon, localized, and dose-dependent [197]. A study by Ondo et al. [56] found a change in the smile of two participants. Shim et al. [54] reported three participants with masticatory difficulties. In a retrospective study of 2036 BoNT treatment sessions for masseter hypertrophy [198], the main complication was perceived muscular weakness and aching, which was observed in 30% of patients. The second-most common complication was bruising due to needle puncture of vessels in the soft tissue, occurring in 2.5% of the injections. All other complications occurred in less than 1% of cases and included headache, asymmetrical smile, limited mouth opening, and xerostomia [198]. Recent studies have reported an association between mandibular bone loss and the use of BoNT in the masticatory muscles [188,189]. However, as described above, the changes in the bone after BoNT injection are not considered an adverse effect but a normal physiological response related to the corrected masticatory force.
An asymmetrical smile may be related to the spread of BoNT into the risorius or zygomatic muscles. Xerostomia can occur due to the spread of BoNT into the parotid gland [147]. Special attention should be paid during injection into the masseter muscle and during extraoral injection to the lateral pterygoid muscle [4,147].
3.4. Functional Movement Disorder
The treatment of functional movement disorders should begin with explaining the diagnosis and ensuring patient understanding [130]. Treatments include antidepressants, psychological therapy in the form of psychodynamic psychotherapy or cognitive behavioral therapy, and transcranial magnetic stimulation [126,130,199]. Comorbid depression, anxiety, and pain may be treated pharmacologically. LaFave et al. [200] reported the most effective therapeutic options for functional movement disorders to be avoiding iatrogenic harm (58%) and educating patients about their diagnosis (53%), based on a recent survey of members of the International Parkinson and Movement Disorder Society.
In a study of 55 patients with functional facial movement disorder, spontaneous remission (a characteristics of functional movement disorder) was observed in 21% of the patients. Notably, 56% of the patients did not show any improvement; 20% exhibited worsened condition; and 20% showed improvements (BoNT injection in five, antidepressants in three, antiepileptics in two, and psychotherapy in one) [128]. In a study of 58 patients with functional stomatognathic movement disorders, symptomatic therapy according to the comprehensive treatment of OMD was selected depending on presenting symptoms included medication, muscle afferent block therapy, BoNT therapy, occlusal splint use, and myomonitor (transcutaneous electro–neural stimulation) [30]. Therapeutic effects were unsatisfactory in most cases in the study [30]. If therapies resulted in ineffective or unsatisfactory responses, patients were referred to psychiatrists or acupuncturists [30].
When patients showed apparent muscle hyperactivity, BoNT therapy improved symptoms considerably [30]. For typical cases of jaw or tongue deviation, BoNT should be administered to the lateral pterygoid or tongue muscles. Additional target muscles include the platysma, orbicularis oris, risorius, mentalis, zygomaticus, and depressor anguli oris muscles [30]. Occlusal splints are occasionally effective for patients with a sensory trick in the oral cavity [158]. Positive effects including immediate improvement just after muscle afferent block therapy or insertion of the splint may be related to suggestibility or the placebo effect, which are typical clinical features in functional movement disorders [30].
Pitfalls
In one study, only 5.2% of patients with functional stomatognathic movement disorders were suspected to have functional movement disorders despite diagnoses by movement disorder specialists [30]. The patients in the study visited 6.2 hospitals over 4.1 years [30]. The entity is frequently misdiagnosed as other psychiatric, neurological diseases.
A multidisciplinary team approach involving a neurologist, psychiatrist, neurosurgeon, physiotherapist, psychotherapist, and oral surgeon is preferable for the diagnosis of and individual therapies for functional stomatognathic movement disorders [30]. However, very few psychiatrists or psychotherapists are willing to treat patients with such conditions [201]. The survey to members of the International Parkinson and Movement Disorder Society [200] suggested frequent treatment barriers, including a lack of physician knowledge and training (32%), lack of treatment guidelines (39%), limited availability of referral services (48%), and cultural beliefs about psychological illnesses (50%). A lack of access to both mental healthcare providers and rehabilitation specialists remains an important limitation for treatment [202].
3.5. Palatal Tremor
Management options for essential palatal tremors include medication (clonazepam, lamotrigine, sodium valproate, and flunarizine) [141]; psychotherapy [203]; and surgical procedures; however, the tinnitus and palatal movements are often refractory [59]. Several case reports and series suggest BoNT is effective in the treatment of palatal tremors [59,204]. One retrospective study included 15 patients with essential palatal tremors, and 2.5 or 5 units of BoNT caused amelioration of symptoms in 85.7% of the cases [59]. BoNT injection into the tensor veli palatini muscle is particularly useful for patients with tinnitus, whereas BoNT injection into the levator veli palatini muscle is efficacious for patient-perceived palatal motion [59].
Pitfalls
The adverse effects of BoNT therapy include voice change, nasopharyngeal regurgitation [58], Eustachian tube dysfunction, and velopharyngeal inadequacy [205]. A well-experienced and knowledgeable clinician should inject BoNT and should be prepared to handle any complications.
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