Clinical manifestations

Presentation and course

Oromandibular dystonia is a focal dystonia manifested by involuntary muscle contractions producing repetitive patterned mouth, jaw, and tongue movements (49; 12; 16; 33; 82). Many patients with oromandibular dystonia initially present with blepharospasm, and blepharospasm often spreads to the oromandibular region, leading to oromandibular dystonia (07). Patients with oromandibular dystonia have difficulty chewing, eating, and speaking because of an inability to open or close their jaw. In addition, there is often lingual dystonia, activated by eating, which causes the tongue to push the food out of the mouth. Because of the eating difficulties, some patients lose weight. In addition to the dysarthria, dysphagia, dysphonia, and respiratory difficulties, many patients with bulbar dystonia display involuntary vocalizations, including humming, grunting, belching, and gasping. In a retrospective review of 240 patients with oromandibular dystonia, the mean age at onset was 51.6 years old, with a 2:1 female predominance and family history of dystonia in six patients (2.5%) (91). Jaw-opening type of oromandibular dystonia was found in 149 patients (62.1%); 48 (20.0%) had the jaw-closing type, 43 (17.9%) had a mixed form of oromandibular dystonia, and lingual dystonia was also present in 64 patients (26.7%).

Oromandibular dystonia may cause a jaw closure with clenching, trismus, and bruxism (60; 110; 99; 13; 61; 105; 72). In a study of 2020 patients with oromandibular dystonia, the typical age at onset was in the 50s, and 70% of cases were female; the perioral musculature was involved in 85%, jaw in 61%, and tongue in 17% (86). Most of the patients were females, and many had associated depression and anxiety. Bruxism, also referred to as teeth-clenching or teeth-grinding, may be a manifestation of oromandibular dystonia or abnormal masticatory muscle activity as part of nocturnal oral parafunction or nocturnal bruxism (see also MedLink article on sleep bruxism by Gerstner). The involuntary movement disorder, whether diurnal or nocturnal, results in chronic jaw clenching (trismus) and tooth grinding (bruxism) (61; 105). Although the cause of bruxism is probably multifactorial, the disorder is often associated with oromandibular dystonia and other neurologic disorders such neuroacanthocytosis, Huntington disease, Tourette syndrome, autism, Rett syndrome, dementing disorders (58), basal ganglia infarcts, and brainstem lesions, as well as jaw injury or surgery and drugs such as the dopamine receptor blocking drugs (neuroleptics), serotonin uptake inhibitors, CNS stimulants, and ecstasy (03; 26). Similar to other dystonias, many patients with bruxism associated with oromandibular dystonia have noted that various maneuvers (sensory tricks) and dental prosthetic devices relieve their jaw spasms.

In addition, involuntary jaw closure, jaw opening, or jaw deviation dystonia may occur and may interfere with speaking and chewing. In contrast to jaw-closing dystonia, jaw-opening oromandibular dystonia tends to be associated with dystonia in other body regions (90). Many patients have noted that various alleviating maneuvers (sensory tricks) and dental prosthetic devices relieve their jaw spasms, particularly jaw closure dystonia (31). In some cases, the involuntary movements occur only during a specific task, such as speaking or reciting prayers (42). Oromandibular dystonia may follow jaw injury or surgery and may be complicated by secondary dental wear and temporal-mandibular joint syndrome (81; 94). In one study of 53 patients with oromandibular dystonia, 90% screened positive for temporal-mandibular joint syndrome (94). Besides primary or peripherally induced dystonia, oromandibular dystonia may be associated with or secondary to a variety of neurodegenerative disorders such as neuroacanthocytosis, Huntington disease (47), basal ganglia infarcts (96), and brainstem lesions (23). Oromandibular dystonia should be differentiated from hemifacial or hemimasticatory spasm, tetany, tetanus, trismus, and mechanical disorder of the jaw or the temporomandibular joint (103; 45; 109; 98; 101; 87; 111). Another condition associated with involuntary jaw movements is Tourette syndrome in which dystonic oromandibular tics may be the main involuntary movements but are usually accompanied by other motor and phonic tics (04).

Prognosis and complications

Although it is difficult to predict the future course of oromandibular dystonia, in most cases, the dystonia remains confined to the oromandibular region. In many cases, however, the dystonia spreads to adjacent structures, causing blepharospasm, cervical dystonia, and other forms of dystonia. Longstanding jaw-closure dystonia may result in secondary temporomandibular joint syndrome.

Clinical vignette

A 61-year-old woman underwent a series of dental procedures, including gingivectomy and braces for six months. Afterwards, she had cosmetic filling of her maxillary teeth, followed by the placement of three separate bridges. On the same day of this last procedure, she noticed abnormal jaw movements that caused displacement of the left bridge. Since that time, she has been unable to wear her lower dentures. Her mouth and jaw movements worsened gradually over the next 16 years. The patient also had mouth soreness on wearing her dentures and had difficulty in speaking clearly due to the painful spasms. Four years prior to our evaluation, her movements occurred only while wearing dentures and completely resolved within 30 minutes after their removal. The movements could be relieved by sensory tricks such as touching her tongue to the top of her mouth, biting her lips, and swallowing. The patient was seen for the last 16 years by various dentists and physicians without any medications or a working diagnosis.

Examination revealed repetitive deviation of the mandible to the left, particularly when speaking and chewing. She had bilateral masseter spasms and considerable difficulty in moving her jaw to the right, particularly when the upper dentures were in place. She was injected with 195 units of botulinum toxin-A over two sessions, and experienced dramatic relief of her symptoms (grade 4 improvement) for about four months; during which time she was able to wear her dentures without any discomfort.

Biological basis

Etiology and pathogenesis

Dystonia is either a symptom of an underlying disorder or a specific disease entity (49; 02). When dystonia occurs as an isolated neurologic disorder without any evidence of cognitive abnormalities, seizures, weakness, sensory, or cerebellar deficit and without other movement disorders, it is classified as primary dystonia. Primary dystonia can be either sporadic or inherited. Secondary dystonias are caused by a specific structural, metabolic, toxic, or other etiology. Secondary dystonia may occur after a specific event, such as head trauma, encephalitis, stroke, brain surgery, or exposure to certain drugs, and in association with a variety of systemic and neurodegenerative disorders (80; 43). Virtually any metabolic or structural lesion of the brain, particularly if it involves the putamen, other basal ganglia, rostral brainstem, and upper cervical lesions, may result in cranial, including oromandibular, dystonia (37). Although genetic predisposition has been suggested to play a role in some cases of secondary dystonia (30), the DYT1 gene mutation is rarely associated with oromandibular dystonia (14). GTP-cyclohydrolase 1 (GCH1) gene mutation was reported in a 49-year-old man with oromandibular dystonia (92).

In contrast, DYT6 dystonia, caused by mutations in the THAP1 gene on chromosome 8p21-q22, in addition to the clinical phenotype of DYT1, also involves the head, jaw, neck, and larynx; it is often associated with oromandibular dystonia (32). The product of the THAP1 gene has been found to be involved with DNA binding and in regulation of endothelial cell proliferation (11). The typical onset is cranial and brachial rather than cervical, with dystonia gradually becoming generalized in all (15). The oldest age at onset was 49 years. Childhood-onset spasmodic dysphonia progressing to generalized dystonia is another presentation of DYT6 (24). In addition to Amish-Mennonite families, DYT6 has also been documented in British patients and other populations (40). In an American series, THAP1 heterozygous mutations were identified in 9 of 36 (25%) DYT1-negative families with early-onset, non-focal primary dystonia (15).

Of the secondary dystonias, Wilson disease and drug-induced (tardive) dystonia are particularly important to recognize because early treatment can result in a complete, or near complete, abolishment of the involuntary movement (93; 95; 108). Oromandibular dystonia may also be a manifestation of levodopa-related dyskinesia (102). Besides central etiologies, which presumably account for the vast majority of dystonias, peripherally induced dystonia caused by an injury is being increasingly recognized as an important cause of oromandibular dystonia (81). Oromandibular dystonia may be also associated with or secondary to a variety of brainstem lesions and neurodegenerative disorders such as neuroacanthocytosis, Huntington disease (97; 47), and rapid-onset dystonia-parkinsonism associated with mutation in the Na/K-ATPase alpha3 subunit (ATP1A3) (51). Bruxism, a form of jaw closure oromandibular dystonia, has also been associated with the use of drugs such as ecstasy and serotonin uptake inhibitors such as venlafaxine (03).

Pathophysiology of dystonia. The pathophysiology of dystonia is not well understood, but progress has been made as a result of novel neurophysiologic and imaging techniques (06; 21; 36; 65). Excessive cocontraction of antagonist muscles, one of the physiological hallmarks of dystonia, is apparently produced by abnormal synchronization of presynaptic inputs to antagonist motor neuron pools (29). Abnormalities in early and late long-latency reflex responses have been found in focal dystonia and can be influenced by botulinum toxin injections, suggesting the involvement of peripheral mechanisms (68). Several investigators have demonstrated increased amplitude and duration of the R1 and R2 blink responses, not only in patients with blepharospasm but also in patients with other dystonias, including oromandibular dystonia (37). These findings have been interpreted as being indicative of enhanced excitatory drive to the rostral brainstem or reduced spinal and brainstem inhibition. Abnormal processing of muscle spindle input has been suggested as an important element in the pathophysiology of dystonia. The frequent co-existence of blepharospasm and oromadibular dystonia supports the notion of a common pathophysiologic mechanism for this cranial dystonia (85).

The involvement of basal ganglia in dystonia is also supported by the finding of reduced glucose metabolism, as demonstrated by PET scans, in the basal ganglia, the frontal projection field of the mediodorsal thalamic nucleus, and in the frontal cortex of patients with primary dystonia (53). Blood flow PET and activation studies suggest that the chief alteration in primary dystonia is overactivity of the planning (rostral) portion of the cortical supplementary motor area, prefrontal area, and the caudate nucleus, whereas the motor executive (caudal) portion of the supplementary motor area and the motor cortex are underactive (19). These findings have been interpreted as evidence of thalamo-frontal disinhibition and abnormal central sensorimotor processing in dystonia (35). In addition to cortical abnormalities, PET and neurophysiologic studies have demonstrated altered function of subcortical structures. Eidelberg and colleagues demonstrated two patterns of metabolic abnormality in patients with dystonia: (1) increased activity in the lentiform nuclei, cerebellum, and supplementary motor area, found in dystonic patients without evident dystonia during sleep (movement-free) and (2) increased metabolic activity in the midbrain, cerebellum, and thalamus, found only in patients who exhibited dystonia at rest while awake (movement-related) (25). Various neurophysiologic and imaging studies provide additional support for the observation that in dystonia there is reduced pallidal inhibition of the thalamus that may explain the overactivity of medial and prefrontal cortical areas and underactivity of the primary motor cortex (06). Pallidal overactivity has been demonstrated in patients with dystonia by microelectrode recordings, and pallidotomy appears to be an effective procedure for patients with dystonia (71; 107).

Pathoanatomy and biochemistry. Although in most patients with dystonia, no specific abnormality can be identified by neuroimaging or autopsy studies, there is convincing evidence supporting a central origin (basal ganglia, brainstem, or both) for this movement disorder. Lesions, particularly in the putamen and globus pallidum internum, have been associated with dystonia (76; 08; 17; 57). Among 240 patients with lesions in the basal ganglia, dystonia was observed in 36% (08). In an anatomic-clinical study using 3-dimensional MRI, "dystonic spasms" were associated with a lesion in the striatopallidal complex, whereas "myoclonic dystonia" was associated with lesions in the thalamus, particularly ventral intermediate and ventral caudal nuclei (63). In another study, using 3-dimensional T1-weighted MRI, striatopallidal dystonia was attributed to lesions within the sensorimotor part of the striatopallidal complex, and thalamic dystonia was associated with lesions in the centromedian or the ventral intermediate nuclei (57).

Imaging studies do not usually show any specific abnormalities, but T2 values on high-field MRI have been found to be significantly higher in the putamen and pallidum of patients with cervical dystonia, as compared to age-matched controls (84). A 10% enlargement of the putamen was found in another study of patients with focal dystonia (09). Although this finding probably reflects a response to the dystonia, it could also indicate early gliosis in the lentiform nucleus.

Only a mild reduction in striatal [18F]dopa uptake was demonstrated in some patients with familial primary dystonia and in dopa-responsive dystonia (70; 77). Dopamine receptor binding, measured by C11 spiperone PET scan, appears normal or slightly increased in the contralateral striatum in patients with idiopathic focal dystonia (62). In contrast to that study, Perlmutter and colleagues found about a 30% reduction in D2 receptor density, as estimated by PET scans of patients with hand dystonia using [18F]spiperone (75).

Only limited information is available on biochemical analyses of the brains of patients with dystonia. The observation that manipulation of the dopaminergic system can produce or ameliorate dystonia has provided evidence for the role of dopamine in the pathogenesis of primary dystonia. Although complex 1 mitochondrial defect has been suggested in idiopathic dystonia (05), a subsequent study demonstrated such defect only in the platelets of patients with focal and not generalized dystonia (83).

A major advance in the understanding of autosomal dystonia has been the identification of a gene mutation (DYT1) in the q32-34 region of chromosome 9 in a large, non-Jewish kindred (56; 59). The mutation consists of a three base-pair deletion in a gene coding for a novel ATP-binding protein in the 9q34 locus, termed “torsinA” (73). In addition to the DYT1 dystonia, several other genetic forms of dystonia have been identified. Mutations in the GTP-cyclohydrolase 1 gene on chromosome 14 (41) have been associated with dopa-responsive dystonia. This form of dystonia, however, is rarely manifested by oromandibular dystonia. Of the 13 types of primary genetic dystonia for which a gene marker or actual gene mutation has been identified, only DYT 7 (mapped to chromosome 18p) and DYT 13 (mapped to chromosome 1p36.13-36.22) dystonias have been associated with cranial, including oromandibular, dystonia (55; 106).

Epidemiology

Based on an epidemiologic study of the population living in Rochester, Minnesota, the incidence of dystonia has been estimated to be two per million persons per year for generalized dystonia, and 24 per million persons per year for focal dystonia (69). The prevalence of dystonia has been estimated to be 3.4 per 100,000 population for generalized and 30 per 100,000 population for focal. No study has specifically addressed the epidemiology of oromandibular dystonia. If bruxism (clenching and teeth grinding) is included as a form of oromandibular dystonia, the prevalence of this form of focal dystonia is probably high, and oromandibular dystonia may be the most frequent form of focal dystonia (13).

Prevention

There is no known way to prevent the development or progression of primary oromandibular dystonia. Tardive oromandibular dystonia, however, can be prevented by avoiding the use of dopamine receptor drugs and by following patients who are taking these drugs closely for early signs of tardive dyskinesia (46).

Differential diagnosis

Table 1 lists the causes of dystonia with emphasis on the causes of oromandibular dystonia.

Table 1. Etiology of Blepharospasm and Oromandibular Dystonia

Oromandibular dystonia is occasionally confused with other facial movement disorders, such as hemifacial spasm (109), facial tics, myokymia, myorhythmia, hemimasticatory spasm, and aberrant regeneration with synkinesis after Bell palsy. Hemifacial spasm is characterized by initially progressive, involuntary, irregular, clonic, or tonic movements of muscles innervated by the seventh (facial) cranial nerve on one side of the face. It often initially involves the orbicularis oculi muscle, followed by gradual spread to other parts of the face. Usually without any identifiable etiology, this peripheral movement disorder has been most frequently attributed to compression of the facial nerve at the root exit zone by an ectopic anatomical or pathological structure, resulting in "ephaptic transmission." Rare cases of bilateral hemifacial spasm have been reported (97). When hemifacial spasm coexists with trigeminal neuralgia, suggesting that both facial and trigeminal nerves are compromised, it is referred to as "tic convulsif." Hemimasticatory spasm is a rare disorder in which painful muscle contractions, frequently associated with hemifacial atrophy, affect the jaw-closing muscles innervated by the trigeminal nerve (masseter). Bilateral hemimasticatory spasm, which would most closely resemble jaw-closing dystonia, has not been reported. Hemimasticatory spasm has been attributed to an abnormal trigeminal hyperexcitability likely induced by a demyelinating lesion of the trigeminal nerve (27).

Diagnostic workup

If primary (idiopathic) oromandibular dystonia is suspected, there is usually no need for diagnostic tests, except possibly for an evaluation for Wilson disease, particularly if the symptoms began before the age of 50 years. When historical or clinical features suggest secondary oromandibular dystonia, neuroimaging studies should be performed to exclude structural abnormalities in the brain and posterior fossa. Furthermore, because patients with neuroacanthocytosis often exhibit oromandibular dystonia and "eating dystonia," examination of blood smear and blood creatine kinase test would be appropriate in this form of dystonia, particularly if there is any other clinical evidence of neuroacanthocytosis. Finally, imaging of the temporomandibular joints to evaluate secondary changes associated with bruxism may be helpful.

For scales used to assess patients with dystonia, see the article titled Rating scales in movement disorders.

Management

Oromandibular dystonia rarely improves with medications, although some patients report modest benefit with anticholinergic drugs (eg, trihexyphenidyl), baclofen, benzodiazepines, and clozapine (38). Injection with botulinum toxin is clearly the most effective therapy for oromandibular dystonia (48; 20; 89; 54; 44). In the Dystonia Coalition study, botulinum toxin injections improved symptoms by more than 50% in approximately 80% of subjects (86). The masseter muscles are usually injected in patients with jaw-closure dystonia. Jaw-opening dystonia is more challenging to treat, but injections into the submental muscle complex or the lateral pterygoid muscles usually provide satisfactory relief in most patients (78). In an open trial, a meaningful reduction in the oromandibular-lingual spasms and an improvement in chewing and speech were achieved in more than 70% of treated patients (50). The improvement was noted within an average of 5.5 days after injection and lasted 11.5 weeks. Patients with dystonic jaw closure responded better than those with jaw-opening dystonia. A temporary swallowing problem was noted in less than one-third of patients initially, but this is now a rare complication due to more experience in targeting the appropriate muscles and adjustment in dosages. Although most of our patients with jaw opening oromandibular dystonia benefit from submental injections, patients with jaw protrusion and lateral deviation have been found to have increased contractions of the lateral pterygoid muscles (67). Botulinum toxin injections provide the most effective relief of oromandibular dystonia, and early treatment with botulinum toxin may prevent dental and other complications, including the temporomandibular joint syndrome and other oral and dental problems (10; 52; 98; 99; 100). A systematic review of botulinum toxin studies in oromandibular dystonia involving 387 patients in nine studies showed that the risk of dystonic movements was 39.30% lower in the treatment group compared to the control group (22). Furthermore, a total of 105 of 387 patients (27.1%) experienced adverse events, most commonly dysphagia.

Trismus with or without bruxism may be effectively treated with botulinum toxin into the masseter and temporalis muscles (104; 34; 72; 88). In a study 23 patients with sleep bruxism confirmed by polysomnography were enrolled in a randomized, placebo-controlled, 1:1, parallel-design trial with open-label extension (72). They were injected with a placebo or 200 units of onabotulinumtoxinA (60 into each masseter and 40 into each temporalis) or placebo and were evaluated at 4 to 8 weeks after the initial treatment visit. Clinical global impression and visual analog scale of change favored active treatment. This study provides class two evidence that botulinum injections into the masseter and temporalis muscles improve subjective bruxism and painful symptoms associated with sleep bruxism. Botulinum toxin injections in the tongue can be very effective in patients with oromandibular dystonia and lingual involvement (112).

Botulinum toxin treatment alleviates bruxism and often prevents or alleviates dental complications and temporomandibular joint syndrome (44). Furthermore, it may facilitate the placement of a percutaneous endoscopic gastrostomy tube (79). Oromandibular involuntary movements caused by hemimasticatory spasms and other disorders, such as Satoyoshi syndrome, have also been successfully treated with botulinum toxin (66). Although most patients with oromandibular dystonia continue to benefit from repeat botulinum toxin injections, some develop secondary nonresponsiveness (01). In patients who are resistant to drug or botulinum toxin treatment, muscle spindle afferent block with intramuscular injection of lidocaine and alcohol has been reported to provide an average 70% improvement in patients with jaw-closure dystonia and 38% improvement in jaw-opening dystonia (113). In some patients who were treated for severe generalized dystonia with pallidotomy, there was a marked improvement in oromandibular dystonia (71). Oromandibular dystonia has also been reported to improve with bilateral pallidal deep brain stimulation (18).