The human skull comprises a pair of temporomandibular joints (TMJs), pivotal connections between the cranium and the lower jaw (mandible) that orchestrate the intricate choreography of mouth opening and closing. A complex gliding joint, the TMJ is the outcome of the harmonious interplay between the mandible's condyle and the temporal bone's squamous portion. Wrapped in fibrous connective tissue, it finds protection within a fibrous capsule spanning from the superior periphery of the temporal joint to the inferior extent of the mandible's neck.
Marking its articular landscape, the temporal bone showcases an anteriorly arched convex articular eminence and a posteriorly concave articular fossa. Meanwhile, the mandible's articulation presents itself through the condyle's uppermost facet. Intervening these mandibular and temporal surfaces is the articular disk—an anatomical partition that bifurcates the joint cavity into the superior and inferior compartments, each hosting distinct movements. The superior compartment accommodates the seamless gliding maneuvers like retrusion and protrusion, while the inferior compartment guides the pivotal hinge actions of elevation and depression.
Fortified by a network of ligaments bridging the mandible to the sphenoid and temporal bones, and bolstered by the muscles governing mastication, the TMJ assumes a critical role. This joint, however, resides within a delicate milieu, ensconced by vital structures that warrant meticulous care to prevent compromise during medical interventions.
Notably, the articular disk, or meniscus, emerges as a biconcave fibrocartilaginous structure integral to the TMJ's harmonious operation. Comprising a substantial anterior band, a delicate intermediate zone, and another substantial posterior band, the meniscus serves as a supple conduit for the mandibular condyle's gliding movement. In the closed mouth posture, the thick posterior band keeps the condyle clear of the temporal bone's articular fossa. Upon mouth opening, the thin intermediate zone emerges, fostering a separation between the condyle and the temporal bone's articular eminence.
The intricate symphony of TMJ movement finds its composers in the muscles of mastication—namely, the masseter, medial and lateral pterygoids, and temporalis. Emerging from the first pharyngeal arch and animated by the mandibular nerve, a branch of the trigeminal nerve, these muscles harmonize to facilitate food mastication, orchestrating mouth closure and lateral tooth motions. However, the TMJ's health can be compromised by parafunctional actions such as clenching and grinding.
The act of mouth opening primarily hinges on gravity, while controlled resistance is administered by the infrahyoid muscles and the platysma. Together, these elements intricately modulate the dynamic tableau of TMJ function.
The syndrome
Temporomandibular disorder(s) (TMD), or temporomandibular joint syndrome, represent an array of pathologies affecting the TMJ and its surrounding structures. These disorders are linked in that they all can cause pain and limit the function of the TMJ. TMD is the most common cause of facial pain after toothache. In the past, many physicians called this condition TMJ disease or TMJ syndrome, but this nomenclature was replaced due to the growing body of scientific research regarding these disorders.TMD was previously known under the eponymous title of Costen syndrome, after Dr. James Costen, who elucidated many aspects of the syndrome as it relates to dental malocclusion. Today, a much more comprehensive view of this condition exists, and the term temporomandibular disorder (TMD) is the preferred term according to the American Academy of Orofacial Pain (AAOP) and most other groups who sponsor studies into its origins and treatment. Interestingly, the National Institute of Dental and Craniofacial Research (NIDCR) puts TMJ and TMD together and refers to them as temporomandibular joint disorder (TMJD). However, the term TMD is preferred and used in this article.
No unequivocal definition of the disease exists and 2 classification schemes are used. The AAOP classification divides TMD broadly into 2 syndromes:
Muscle-related TMD (myogenous TMD), sometimes called TMD secondary to myofascial pain and dysfunction
Joint-related (arthrogenous) TMD, or TMD secondary to true articular disease
Of note, these 2 types often coexist in one patient, making diagnosis and treatment more challenging. In addition, due to the anatomy of the mandible, dysfunction of one joint can impact the contralateral joint, and bilateral symptoms are common.
Myogenous TMD is more common. In its pure form, it lacks apparent destructive changes of the TMJ on radiograph and can be caused by multiple etiologies such as bruxism and daytime jaw clenching.
Arthrogenous TMD can be further specified as disk displacement disorder, chronic recurrent dislocations, degenerative joint disorders, systemic arthritic conditions, ankylosis, infections, and neoplasia. The most common is displacement disorder, which has two subtypes: anterior displacement with reduction and anterior displacement without reduction.
The Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) also exist.[1] The RDC/TMD criteria are composed of algorithms that aid in obtaining a diagnosis along 2 separate axes. The Axis I score provides what is considered the clinical diagnosis, and the Axis II score provides an assessment of mandibular function, psychological status, and level of TMD-related psychosocial disability. This discussion emphasizes the terminology and viewpoint of the AAOP approach. However, the authors are mindful of the important features of the RDC/TMD system. As is the case for most diseases and syndromes, the effect on the patient's life is a major feature of the problem and the psychological and psychosocial aspects are of great importance, and consideration of these factors necessitates a multidisciplinary approach in difficult cases.
In myogenous temporomandibular disorder, the most common cause of the symptomatology (ie, pain, tenderness, and spasm of the mastication muscles) is muscular hyperactivity and dysfunction due to either parafunctional activities, or malocclusion of variable degree and duration. Psychological factors may also play a role. Studies have also linked regulatory pain pathways and local spread of pain signals within the cells of the spinal trigeminal nucleus to the severity, chronicity, and location of pain.
In TMD of articular origin, disk displacement is the most common cause. Abnormal anterior displacement and interposition of the posterior band between the condyle and the eminence cause pain, pops, and crepitus. If the anteriorly displaced posterior band spontaneously returns to the normal position before the completion of jaw opening, it is called anterior displacement with reduction. It must be emphasized, however, that the presence of pops and clicks denoting anterior displacement with reduction does not necessarily denote pathology and studies of healthy populations have found these signs in a large percentage of individuals who did not later develop symptoms of TMD.
The sudden reduction of the posterior band causes the characteristic pop or click. If the posterior band remains anteriorly displaced at all times during jaw opening, it is called anterior displacement without reduction; full jaw opening may not be possible, and the distance between the incisors is usually less than 25mm. The jaw will usually deviate to the side of pathology. Inability to attain a jaw opening of more than 10 mm is known as closed lock. In TMD of articular origin, the spasm of the mastication muscle is secondary in nature.
The other causes of arthrogenous TMD are diseases such as degenerative joint disease, rheumatoid arthritis, ankylosis, dislocations, infections, and neoplasia, the pathophysiology of which are self-explanatory. One study found that, in patients with chronic inflammatory connective tissue disease, the pain on mandibular movement and tenderness on posterior palpation of temporomandibular joints was related to the level of tumor necrosis factor alpha in the synovial fluid.
In a separate study, interleukin 1 receptor antagonist (IL-1ra) and soluble IL-1 receptor II (sIL-1RII) in the synovial fluid and blood plasma of patients with TMJ involvement of polyarthritis appeared to influence the TMJ inflammation.[2]
An important development may connect some of the psychosocial aspects of the disease to underlying neurobiology. This is the discovery that the likelihood of a patient being diagnosed with TMD is related to genetic variations in the gene coding for catecholamine-O-methyltransferase (COMT), a gene that relates in to some aspects of pain sensitivity.
Temporomandibular disorder is a commonly seen condition in primary care and dentistry practice. According to some authorities, as many as 75% of the people in the United States population will at some time have some of the signs and symptoms of TMD; however, all of these individuals are not believed to have TMD. Between 5% and 10% of Americans may sufficiently fulfill the criteria to merit a diagnosis of TMD.
Race-, sex-, and age-related demographics
In a study of young women aged 19–23 years, facial pain and jaw symptoms related to TMD were noted more frequently in Caucasians than in African Americans. Such symptoms also had an earlier onset in Caucasians.[3]
Temporomandibular disorder primarily affects women with a male-to-female ratio of 1:4.
Highest incidence is among young adults, especially women aged 20–40 years.
Most cases of temporomandibular disorder (TMD) respond to simple treatment and the prognosis is good. Symptoms usually remit with simple care. In cases of secondary involvement of temporomandibular joint (TMJ), the prognosis depends on the primary disease. A second opinion should be obtained in cases in which irreversible treatment is being considered.
The pathology producing the pain and dysfunction should be discussed with the patient. Patients should be told about the possible prognosis of their problem. Myofascial pain and dysfunction tends to have a self-limiting course and needs simple treatment; even though these patients may have recurrences, the symptoms generally are controlled by simple treatment. A patient with TMD secondary to degenerative joint disease should be made aware of the signs of further deterioration such as increasing pain, further limitation of movement, and increased joint sounds.
Self-care includes simple measures such as soft diet with gradual progression to normal diet over 6–8 weeks, avoiding large bites and clenching of teeth, avoiding chewing gum and pens, keeping jaw relaxed, yawning against pressure, massage of jaw and temple muscles, use of moist heat, avoiding cradling the phone between ear and shoulder, good sleep posture with adequate neck support, and passive or active range of motion exercises.
For excellent patient education resources, see eMedicineHealth's patient education article Temporomandibular Joint (TMJ) Syndrome.
A comprehensive, chronological history and physical examination of the patient, including dental history and examination, is essential to diagnose the specific condition to decide further investigations, if any, and to provide specific treatment.
Patients may have a history of heavy computer use as this has been found to be associated with development of TMD.[4]
About one third of patients have a history of psychiatric problems.
Patients may have a history of facial trauma, poor dental care, and/or emotional stress.
Patients with chronic eating disorders have a high prevalence of TMD.
Many patients with TMD also have neck and/or shoulder pain.
The practitioner should inquire about daytime or nighttime clenching. Daytime clenching has a stronger association with TMD than night time bruxism.[5]
A positive association may be observed between smoking and the occurrence of TMD in women younger than 30 years, although this association may be explainable by other factors (eg, stress levels).[6]
The patient may complain of any of the following symptoms:
Pain: Pain is usually periauricular, associated with chewing, and may radiate to the head but is not like a headache. It may be unilateral or bilateral in myofascial pain and dysfunction, and usually is unilateral in TMD of articular origin, except in rheumatoid arthritis. The pain is often described as a variable deep ache with intermittent sharp pain with jaw movement.
Click, pop, and snap: These sounds usually are associated with pain in TMD. The click with pain in anterior disk displacement is due to sudden reduction of the posterior band to normal position. An isolated click is very common in the general population and is not a risk factor for development of TMD.
Limited jaw opening and locking episodes: The lock can be open or closed; open lock is inability to close the mouth and is seen when the mandibular condyle dislocates anteriorly in front of articular eminence. Closed lock is an inability to open the mouth because of pain or disk displacement.
Headaches: The pain of TMD is not like a usual headache. The TMD may act as a trigger in patients prone to headaches. TMD involving muscle pain predisposes to migraines and chronic daily headaches and the more painful the TMD, the more likely it is to be associated with headache.[7, 8] Some patients may have a history of headaches resistant to treatment; therefore, the TMD trigger should not be overlooked in such patients.[9]
Otologic symptoms such as earache, decreased hearing acuity, and tinnitus.[10]
Patients with TMD have a higher prevalence of other painful conditions, and symptoms such as headache should be explored, diagnosed, and treated according to current guidelines as a primary disorder when they meet the diagnostic criteria for a specific condition.
Forward head posture (this has been shown to displace the condyles posteriorly)
Jaw malocclusion, abnormal dental wear, and poor dentition
Visible clenching or spasm of the ipsilateral neck musculature
Examination
Joint range of motion: The examiner should evaluate jaw opening and closure as well as lateral deviation bilaterally. Normal range of motion for opening is 5 cm and lateral mandibular movement is normally 1 cm. Patients with TMD usually have reduced opening.
Palpation: The TMJ is best palpated laterally as a depression below the zygomatic arch and 1-2 cm anterior to the tragus. The posterior aspect of the joint is palpated through the external auditory canal. The joint should be palpated in both open and closed positions and also both laterally and posteriorly. While palpating, the examiner should feel for muscle spasm, muscle or joint tenderness, and joint sound. The muscles palpated as a part of complete TMJ examination are masseter, temporalis, medial pterygoid, lateral pterygoid, and sternocleidomastoid. In isolated myofascial pain and dysfunction, joint tenderness and joint click are usually absent.
Etiology is multifactorial and includes malocclusion, jaw clenching, bruxism, personality disorders, increased pain sensitivity, and stress and anxiety; in most patients more than one factor is present.
Significance of neuropsychiatric factors has been recognized during the past few years.
Many patients also tend to score high on obsessive-compulsive scale and have increased levels of disease conviction
Arthrogenous TMD (internal derangements, arthralgias, osteoarthritis, and osteoarthrosis)
Of the causes of arthrogenous TMD, disk displacement is the most common.
Other diseases such as degenerative joint disease, polyarthritides such as rheumatoid arthritis, ankylosis, dislocation, infection, neoplasia, and congenital anomalies may contribute to pain.
In 2005, The National Institute of Dental and Craniofacial Research (NIDCR) began a 7-year clinical study, the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) study, aimed at identifying risk factors for development of TMD.[11] The study enrolls individuals who do not presently have TMD, and it will assess them by physical, psychological, and biochemical testing (including genetic screening) to determine the factors that lead to the development of TMD.
This study, with subsequent analysis of cohorts, has been published and has elucidated some factors appertaining to TMDs. There are genetic variants associated with TMDs, but no single nucleotide polymorphisms could be identified. Candidate gene associations with respect to nociception have been found and these include SCNA1 (voltage-gated sodium channel, type I, alpha subunit), ACE2 (angiotensin I-converting enzyme 2), MPDZ, (heat pain temporal summation with multiple PDZ domain protein), and APP (amyloid-beta precursor protein) Unfortunately, no causality has been firmly established.
If a systemic illness is suspected to be the cause of temporomandibular disorder (TMD), lab work is required. CBC may be done if infection is suspected for elevated white blood cell count. Inflammatory markers such as CRP and ESR, rheumatoid factor (RF), antinuclear antibody (ANA), and other specific antibodies are checked if rheumatoid arthritis, temporal arteritis, or a connective tissue disorder is suspected. Uric acid should be checked if suspicious for gout exists. Pseudogout has also been reported in the temporomandibular joint (TMJ). Arthrocentesis is required to demonstrate specific crystals.
Conventional radiography is the most utilized imaging study. It is simple, evaluates bony structures, and in most cases is sufficient. It involves specific techniques and views such as modified Schuller views of each TMJ, both open mouth and closed mouth. Radiographic findings in TMJ depend on the etiology of TMD; in cases of rheumatoid arthritis and seronegative spondyloarthropathies, plain films show erosions, osteophytes, subchondral bony sclerosis, and condylar-glenoid fossa remodeling.
Dynamic high-resolution ultrasonography allows for visualization of the morphological elements and the functions of the TMJ, articular disk, mandibular condyle, and lateral pterygoid muscle. It is useful in the evaluation of internal derangements of the TMJ. One study found that the accuracy of prospective interpretation of high-resolution sonograms of internal derangement, disk displacement with reduction, and disk displacement without reduction was 95%, 92%, and 90%, respectively.[12]
CT scans can explore both bony structures and muscular soft tissues. Of interest, there is utility with cone beam computed tomography (CBCT). The patient is scanned with the mouth open and closed. Specifically, CBCT can aid in the diagnosis of osteoarthritis, rheumatoid arthritis, synovial chondromatosis, and neoplastic disorders.[13]
MRI should be used as the study of choice if an articular or meniscal pathology is suspected and an endoscopic or surgical procedure is contemplated, or in the case of traumatic TMD.
In one study, MRI was capable of identifying the meniscus in all cases, together with its morphology, signal, location, and movements during opening and closing of the mouth.
Disk dislocations were always identified correctly, and simultaneous study of both TMJ allowed the joints and their motion to be compared and asymmetries detected. The authors observed a high degree of agreement between MRI, arthroscopic, and surgical findings and concluded that MRI should be the study of choice in the evaluation of TMJ disease.
Quantitative analysis of occlusal strain and stress can be can be helpful by using photoplastic phenomenon of some polymers. Results of strain analysis can help harmonize static and kinematic occlusal patterns by detecting and eliminating prematurities and interferences. Stress analysis helps to understand the temporomandibular mechanical relationship.
Cephalometric analysis by the Delaire method allows for specific craniofacial morphotypic criteria to be defined.
Diagnostic arthroscopy is an invasive diagnostic approach and should be used mainly in patients suffering from internal TMJ derangements recalcitrant to conservative measures. MRI is suggested to be obtained prior to arthroscopy.
Most temporomandibular disorders (TMDs) are self-limiting and do not get worse. Simple treatment, involving self-care practices, rehabilitation aimed at eliminating muscle spasms, and restoring correct coordination, is all that is required. Nonsteroidal anti-inflammatory analgesics (NSAIDs) should be used on a short-term, regular basis and not on an as needed basis.[14]
On the other hand, treatment of chronic TMD can be difficult and the condition is best managed by a team approach; the team consists of a primary care physician, a dentist, a physiotherapist, a psychologist, a pharmacologist, and in small number of cases, a surgeon. The different modalities include patient education and self-care practices, medication, physical therapy, splints, psychological counseling, relaxation techniques, biofeedback, hypnotherapy, acupuncture, and arthrocentesis.
Medications
Commonly used medications include NSAIDs, muscle relaxants, and tricyclic antidepressants. More recently, injections of botulinum toxin[15, 16] have been used, in some cases as an adjunct to arthrocentesis (see Arthrocentesis).
Ibuprofen and naproxen are commonly used NSAIDs. They work best when given on a regular basis for a period of 2-4 weeks with a gradual taper rather than a prn basis. Narcotics are reserved for patients with severe acute pain and should be used sparingly.
The commonly used muscle relaxants are diazepam, methocarbamol, and cyclobenzaprine. The lowest effective dose should be used initially. Adverse effects include sedation, depression and addiction.
Tricyclic antidepressants, in low doses, have been used effectively for a long time in chronic painful conditions. They act by inhibiting pain transmission and also may reduce nighttime bruxism. Amitriptyline and nortriptyline, in small doses, are the most common tricyclic antidepressants used for chronic painful conditions.
Botulinum toxin is used both as a single treatment[17] and in conjunction with arthrocentesis[18] (see Arthrocentesis). No controlled studies exist of the use of this medication in TMD. As noted in the article by Schwartz and Freund, care must be taken to isolate the muscle properly and inject appropriate doses. The authors know of no large-scale double-blind controlled trials on this subject, but some open-label studies have looked promising. A promising controlled study on facial pain associated with masticatory hyperactivity did show a significant benefit to botulinum toxin.[19] However, the patients were not diagnosed with TMD and it is not possible to tell which patients fulfilled diagnostic criteria for TMD.
Occlusal splints
These are known as nightguards, bruxism appliances, or orthotics. Various kinds of splints are available and can be classified into 2 groups—anterior repositioning splints and autorepositional splints. Physiologic basis of the pain relief provided by splints is not well understood. Factors such as alteration of occlusal relationships, redistribution of occlusal forces of bite, and alteration of structural relationship and forces in the temporomandibular joint (TMJ) seem to play some role.
Autorepositional splints, also known as muscle splints, are used most frequently. Some sort of pain relief is seen in as many as 70–90% of patients using splints. In acute cases the splint may be worn 24 hours a day for several months and as the condition permits, worn at night only.
Hyaluronic acid injections
There have been some recent musings in the literature about the effectiveness of this treatment for TMD. A meta-analysis was published that drew inconclusive results regarding the effectiveness of this treatment, citing that it seemed to be comparable to treatment with occlusal splints. This study did comment on the fact that there was a response compared to placebo, but more data needs to be accumulated and examined prior to drawing any conclusions concerning the effectiveness of hyaluronic acid injections for the treatment of TMD.[20] Another recent study examined the effectiveness of hyaluronic acid injections in various forms of osteoarthritis and they too came to the conclusion that its effectiveness is questionable and is not superior to intra-articular injections of corticosteroids.[21]
The treatment of chronic TMD is difficult and it may appropriate during the course of the disease to discuss surgical treatment options.
Arthrocentesis
A 22-gauge needle is inserted gently in the superior joint space and a small amount of saline is injected to distend the joint space, after which the fluid is withdrawn and evaluated. The joint then is redistended and a second needle is placed in the same joint space to lavage the joint; steroids and/or local anesthetics can be injected into the joint space at the conclusion of the procedure.
Simple washing of the upper compartment of TMJ using arthrocentesis has been very effective in patients with a history of condylomeniscal incoordination; results have been comparable to those of arthroscopic surgery.
The benefit of this treatment brings into question the significance of disk position in the etiology of TMD.
Arthroscopic surgery
Indications include internal derangements, adhesions, fibrosis, and degenerative joint diseases.
It appears to be as efficient as open surgical procedure and has the added benefits of fewer severe complications and less surgical morbidity.[22] One retrospective short-term study found it to be safe, minimally invasive, and an effective treatment method, with 80% of patients reporting reduced pain and increased range of motion; in acute TMJ lock, however, arthroscopy and arthroscopic lysis and lavage of the upper compartment of TMJ produce comparable success rates.
In one study, only 10.3% of 301 patients who underwent arthroscopic lysis and lavage had complications. More than 80% of complications were otological in nature; neurological complications were seen in 5 cases—of which 3 were fifth cranial nerve injury and 2 were seventh cranial nerve injury.
Open surgery
Hemijoint replacement has been performed with good result in those patients with advanced osteoarthritis of the TMJ.
Total alloplastic replacement (arthroplasty) has been shown to provide a safe and effective treatment for reankylosis of the TMJ.[23]
Open surgery was the main surgical option in the 1970s and 1980s, and the most common procedure was disk repositioning and plication. In cases of severe disk damage, procedures such as disk repair and removal were done using artificial or autogenous material.
Myrhaug technique: Described in 1951, this procedure, by resecting the temporal condyle, creates a permanent and reducible chronic dislocation of the joint. One study found 70% good or excellent results in 60 patients. The main indications include (1) TMD not responding to all other treatments and (2) chronic subdislocations of one or both TMJ.
Physical therapy: Apart from patient education and pain control, the main goal of physical therapy is to stabilize the joint and restore its mobility, strength, endurance, and function. Common modalities used to accomplish these goals are the following:
Relaxation training using electromyographic (EMG) biofeedback: The patient first is educated about the contribution of stress and muscular hyperactivity to pain. An EMG monitor provides instant feedback to patients about the state of their muscle activity and allows the patient to easily correlate pain with hyperactivity of the muscles and decrease in pain with relaxation.
Friction massage: The hypothesis is that temporary ischemia and resultant hyperemia, produced by firm cutaneous pressure during massage, helps inactivate trigger points. Friction massage also may help disrupt small fibrous adhesions in the muscle formed as a result of surgery, injury, or prolonged restricted motion.
Ultrasonic treatment: ultrasonic waves produce tissue heating at a deeper level than moist heat; this increase in local tissue temperature leads to increase in blood flow and removal of metabolic byproducts responsible for pain and may help decrease adhesions by disrupting collagen cross-linkage. It also may help decrease intra-articular inflammation. To be effective, ultrasonic treatment should be done every other day, using about 1 watt/cm2 for approximately 10 minutes over the affected muscles and joints.
Transcutaneous electronic nerve stimulation: Electronic stimulation of superficial nerve fiber overrides the pain input from mastication muscles and TMJ, causing release of endogenous endorphins. In some patients it provides longer duration of pain relief than the time during which the stimulation is actually applied.
Cognitive-behavioral treatment: This consists of hypnosis, cognitive coping skills, and relaxation. Hypnotic susceptibility correlates with reductions in reported pain.
Psychology: Chronic painful conditions worsen any preexisting anxiety or depression. In appropriate settings, psychological counseling may provide benefit.
Medications are helpful only for symptomatic relief and should be used only for short periods. NSAIDs, whenever used, should be administered on a short-term regular basis and not as needed.
Clinical Context:
For relief of mild to moderately severe pain; inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which is responsible for prostaglandin synthesis.
These agents have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action is not known, but they may inhibit cyclooxygenase activity and prostaglandin synthesis. Other mechanisms may exist as well, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell-membrane functions.
Clinical Context:
Skeletal muscle relaxant that acts centrally and reduces motor activity of tonic somatic origins, influencing both alpha and gamma motor neurons. Structurally related to tricyclic antidepressants; therefore, has some of same limitations.
By binding to specific receptor sites, these agents appear to potentiate the effects of GABA and facilitate inhibitory GABA neurotransmission and other inhibitory transmitters.
Clinical Context:
One of several toxins produced by Clostridium botulinum. Blocks neuromuscular transmission through a 3-step process, as follows: (1) blockade of neuromuscular transmission; botulinum toxin type A (BTA) binds to the motor nerve terminal. The binding domain of the type A molecule appears to be the heavy chain, which is selective for cholinergic nerve terminals. (2) BTA is internalized via receptor-mediated endocytosis, a process in which the plasma membrane of the nerve cell invaginates around the toxin-receptor complex, forming a toxin-containing vesicle inside the nerve terminal. After internalization, the light chain of the toxin molecule, which has been demonstrated to contain the transmission-blocking domain, is released into the cytoplasm of the nerve terminal. (3) BTA blocks acetylcholine release by cleaving SNAP-25, a cytoplasmic protein that is located on the cell membrane and that is required for the release of this transmitter.
The affected terminals are inhibited from stimulating muscle contraction. Toxin does not affect synthesis or storage of acetylcholine or conduction of electrical signals along the nerve fiber. Typically, a 24-72 h delay between administration of toxin and onset of clinical effects exists, which terminate in 2-6 mo. This purified neurotoxin complex is a vacuum-dried form of purified BTA, which contains 5 ng of neurotoxin complex protein per 100 U.
Treats excessive, abnormal contractions associated with blepharospasm. BTA has to be reconstituted with 2 mL of 0.9% sodium chloride diluent. With this solution, each 0.1 mL results in 5 U dose. Patient should receive 5-10 injections per visit. Must be reconstituted from vacuum-dried toxin into 0.9% sterile saline without preservative using manufacturer's instructions to provide injection volume of 0.1 mL; must be used within 4 h of storage in refrigerator at 2-8°C. Preconstituted dry powder must be stored in freezer at < 5°C.
Reexamine patient 7-14 d after initial dose to assess for response. Increase doses 2-fold over previous one for patients experiencing incomplete paralysis of target muscle. Do not exceed 25 U when giving it as single injection or 200 U as cumulative dose in 30-d period. For the purpose of TMD treatment, studies are limited and the medication is not approved. The dosing approach to specific muscles, such as they are known, is given in the article by Schwartz and Freund.
Shaheen E Lakhan, MD, PhD, MS, MEd, FAAN, Clinical Professor of Neurology, Western University of Health Sciences
Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cleveland Clinic; UCLA; MGH; California University of Science and Medicine; Carilion Clinic; Sage Therapeutics; The Learning Corp; Zogenix; Fern Health; Thriveworks; Click Therapeutics; Neurocrine; NeuroSport; SpineThera; Shaheen E. Lakhan, MD.
Specialty Editors
Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Chief Editor
Robert A Egan, MD, NW Neuro-Ophthalmology
Disclosure: Received honoraria from Biogen Idec and Genentech for participation on Advisory Boards.
Additional Contributors
Charles F Guardia, III, MD, Instructor in Neurology, Department of Neurology, Dartmouth Hitchcock Medical Center, Geisel School of Medicine at Dartmouth; Associated Neurologists, Nuvance Health
Disclosure: Nothing to disclose.
Joseph Rios, MD, Assistant Professor, Department of Medical Education, University of Central Florida College of Medicine
Disclosure: Nothing to disclose.
Michael J Schneck, MD, MBA, Vice Chair and Professor, Departments of Neurology and Neurosurgery, Loyola University, Chicago Stritch School of Medicine; Associate Director, Stroke Program, Director, Neurology Intensive Care Program, Medical Director, Neurosciences ICU, Loyola University Medical Center
Disclosure: Nothing to disclose.
Stephen A Berman, MD, PhD, MBA, Professor of Neurology, University of Central Florida College of Medicine
Disclosure: Nothing to disclose.
Acknowledgements
The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors Arun Chaudhary, MD; Jeffrey Appelbaum, DO; and Jennifer Ault, DO, DPT to the development and writing of this article.
Sasaki J, Ariji Y, Sakuma S, et al. Ultrasonography as a tool for evaluating treatment of the masseter muscle in temporomandibular disorder patients with myofascial pain. Oral Radiol. 2006. 22:52-7.
