Clinical use of botulinum toxins in oral and maxillofacial surgery

Botulinum toxin (BTX) is a bacterial toxin that could be used as a medicine. Clinical applications of BTX have been expanding over the last 30 years and novel applications reported. Its mechanism of inhibiting acetylcholine release at neuromuscular junctions following local injection is unique for the treatment of facial wrinkles. Other dose-dependent anti-neuroinflammatory effects and vascular modulating properties have extended its spectrum of applications. Conditions such as temporomandibular joint disorders, sialorrhea, headache and neuropathic facial pain, muscle movement disorders, and facial nerve palsy could also be treated with this drug. Further applications of BTX are likely to be developed. This paper reviews the established and emerging applications of BTX in the field of oral and maxillofacial surgery. An overview of the pharmacology, toxicity and preparations of the agent is given.

Purified botulinum toxin (BTX) was the first bacterial toxin used as a medicine. Since its introduction into clinical use, over 30 years ago, it has become a versatile drug in various fields of medicine. The clinical applications of BTX have been expanding and novel applications developed.

BTX is widely used in cosmetic applications for the treatment of facial wrinkles after local injection, but conditions such as temporomandibular joint disorders, sialorrhea, headache and neuropathic facial pain, muscle movement disorders, and facial nerve palsy could be treated with this drug. Many other indications are under investigation, and further applications for BTX are likely to be developed . In the maxillofacial region, most studies on the use of BTX are of low quality (noncomparative, non-randomized trials), but the overall results were promising.

In this review, established and emerging applications of BTX in the field of oral and maxillofacial surgery are discussed. Emphasis is placed on the mechanism of action and outcome of treatment in different clinical situations. An overview of the pharmacology, toxicity and different preparations of the agent is given.

History

The idea of a possible therapeutic use for botulinum toxin (BTX) was first developed by the German physician and poet Justinus Kerner (1786–1862); he called it ‘sausage poison’. In 1870, Muller, another German physician, coined the name botulism. The Latin form is botulus , which means sausage .

In 1897, Emile van Ermengem investigated an epidemic of botulism in Ellezelles, Belgium, after the consumption of raw ham. He isolated the bacteria from the ham and produced the disease in laboratory animals by injecting the toxin produced by the organism .

BTX was developed as a biological weapon by many countries in the twentieth century . Although many countries stopped research related to biological weaponry after signing the Biological and Toxin Weapons Convention, purification of BTX for medical use continued .

A therapeutic use for botulinum toxin type-A (BTX-A) was first studied in primates by Scott et al in 1973 . In the late 1970s, the toxin was introduced as a therapeutic agent for the treatment of strabismus . Since then, its therapeutic applications have expanded into many different fields, often with innovative treatments and surprising results.

BTX was first used for treating facial wrinkles and aging skin in 1988, but its widespread cosmetic use did not occur until the mid-1990s . There was much speculation about the storage, dilution, delivery methods and treatment doses. In maxillofacial surgical practice, Niamtu reported on the cosmetic use of BTX for facial rhytids and dynamic lines in 1999 and 2000 . During the mid- and late-1990s, BTX was used for lateral canthal lines (crow’s feet), platysmal banding, orbicularis oris injection, masseter muscle injection and the treatment of temporomandibular disorders (TMDs). Later, there were many attempts to use BTX for different clinical situations in oral and maxillofacial surgery.

Bacteriology

Clostridium species bacteria are sporulating, obligate anaerobic, Gram-positive bacilli. The spores of C. botulinum are ubiquitous, distributed widely in soil and marine sediments worldwide and often found in the intestinal tract of domestic grazing animals .

Under appropriate environmental or laboratory conditions, spores can germinate into vegetative cells that will produce toxin. C. botulinum grows and produces neurotoxin in the anaerobic conditions frequently encountered in the canning or preservation of foods .

Seven different strains of Clostridium have been described (designated A, B, C (1 and 2), D, E, F and G), and each produces a distinct neurotoxin identified by the corresponding letter of the bacterial strain producing it, so, there are 7 distinct neurotoxins (BTX-A, -B, -C, -D, -E, -F, -G) . Humans can be affected by the toxins of 5 strains (A, B, E, F and G) and are not affected by the toxins of strains C and D . All 7 toxins may potentially cause botulism in humans given a high enough exposure . All 7 neurotoxins are structurally similar but immunologically distinct . There is some serum cross-reactivity among the serotypes because they share some sequence homology with one another as well as with tetanus toxin .

Bacteriology

Clostridium species bacteria are sporulating, obligate anaerobic, Gram-positive bacilli. The spores of C. botulinum are ubiquitous, distributed widely in soil and marine sediments worldwide and often found in the intestinal tract of domestic grazing animals .

Under appropriate environmental or laboratory conditions, spores can germinate into vegetative cells that will produce toxin. C. botulinum grows and produces neurotoxin in the anaerobic conditions frequently encountered in the canning or preservation of foods .

Seven different strains of Clostridium have been described (designated A, B, C (1 and 2), D, E, F and G), and each produces a distinct neurotoxin identified by the corresponding letter of the bacterial strain producing it, so, there are 7 distinct neurotoxins (BTX-A, -B, -C, -D, -E, -F, -G) . Humans can be affected by the toxins of 5 strains (A, B, E, F and G) and are not affected by the toxins of strains C and D . All 7 toxins may potentially cause botulism in humans given a high enough exposure . All 7 neurotoxins are structurally similar but immunologically distinct . There is some serum cross-reactivity among the serotypes because they share some sequence homology with one another as well as with tetanus toxin .

Structure and Toxicity

Toxins produced by clostridial bacteria are high-molecular-weight protein complexes that include 3 key proteins: a 150-kDa toxin, a non-toxin hemagglutinin protein, and a non-toxin non-hemagglutinin protein. The 150-kDa toxin is composed of a 100-kDa heavy chain and a 50-kDa light chain. Disulfide and noncovalent bonds link the heavy and light chains, and both chains are required for neurotoxicity .

BTX is the most toxic material known. It is 4 times more lethal in mice than tetanus toxin, 1 × 10 more lethal than curare, and 100 × 10 more lethal than sodium cyanide . The estimated human dose (assuming a weight of 70 kg) of type A toxin lethal to 50% of an exposed population (the LD50) is estimated, based on animal studies, to be approximately 0.09–0.15 μg by intravenous administration, 0.7–0.9 μg by inhalation and 70 μg by oral administration . Based on findings from primate studies, human LD50 for intramuscular BTX injection is estimated at 2500–3000 U for a 70-kg adult (35–40 U/kg).

Mechanism of Action

BTX is a protease that causes temporary chemical denervation of skeletal muscle by blocking the Ca +2 -mediated release of acetylcholine from nerve endings of alpha and gamma motor neurons (myoneural junction), producing a transient dose-dependent weakening of the muscle activity rendering it nonfunctional without systemic effects . This inhibition of muscular contraction is believed to be followed by the sprouting of new axon terminals, which results in synaptic regeneration and the reestablishment of neuromuscular transmission .

The 7 neurotoxins have different specific toxicities, different durations of persistence in nerve cells , and different potencies . All BTX serotypes, ultimately, inhibit acetylcholine release.

The area of flaccidity produced may be larger than the area of muscle denervated as a result of postulated paralysis of gamma motor neurones, so the output of the muscle spindles is reduced leading to reduced muscular contraction at adjacent sites within the injected muscle . Weakening of surrounding muscles not injected may also occur because of toxin diffusion. Animal studies have demonstrated that BTX-A diffuses across fascial planes to surrounding muscles .

Clinical effect occurs within approximately 3–7 days (typically seen after 1–3 days) after administration, followed by 1–2 weeks of maximum effect, which then levels off to a moderate plateau until full nerve recovery within 3–6 months (typically at approximately 3 months) .

Preparations

A number of BTX preparations have been approved in different countries. Currently, there are 6 different BTXs available on the market, 5 contain BTX-A (Botox, Dysport, Xeomin, Prosigne and PurTox) and the other contains BTX-B (Myoblocs/NeuroBlocs). Approval procedures are complex and vary between preparations and countries, but, in general, Botox has garnered the most approvals worldwide, followed by Dysport .

Treatment doses of BTX vary depending on the brand of toxin used. The dose given for any toxin refers only to that particular preparation and does not readily transfer to doses of other products, even if they are of the same toxin serotype. These ratios should be applied with extreme caution because different preparations may have different efficacy in different parts of the body .

BTX-A

Botox (Allergan Inc, USA): BTX-A (originally called ‘Oculinum’) was first used in humans in 1968 to treat strabismus . In 1991, Allergan Inc. purchased several batches of this purified BTX-A, and the agent was given the name Botox .

Botox is the only available BTX product approved for cosmetic use in North America. It is specifically approved for the therapeutic treatment of strabismus, blepharospasm, cervical dystonia and axillary hyperhidrosis. There are reports of Botox specifically improving patient self-perception .

Each vial of Botox contains 5 ng (100 U) of air-dried toxin, with 1 unit (U) equal to the median amount necessary to kill 50% of female Swiss-Webster mice weighing 18–20 g each after intraperitoneal injection (LD50) . Each vial contains 500 μg of albumin and 900 μg of sodium chloride .

Dysport (Ipsen Limited, UK) is another BTX-A product approved for cosmetic use, which is marketed and sold in many European countries as well as Russia, New Zealand, Mexico, Brazil, Argentina and Vietnam . Each vial contains 12.5 ng (500 U) of air-dried toxin, 125 μg of albumin, and 2.5 mg of lactose . Dysport comes from a different type A strain of bacteria than Botox and doses are not equivalent. Direct comparisons of Botox and Dysport in animal studies suggest that the equivalence doses are 1 U Botox to 2.5–5 U Dysport, though in humans, this conversion is largely an estimate .

Xeomin (NT-201; Merz Pharmaceuticals GmBH, Germany), packaged as a freeze-dried powder, is a purified BTX-A that is free of the accessory complexing proteins (hemagglutinin and nonhemagglutinin) found in the other BTX-A products . It is reported to be less immunogenic than other BTX-A products, making it useful when large amounts of toxin are required for extended periods . Animal studies support this, but reliable human immunogenicity data are not available .

Many studies have found that Botox and Xeomin have similar dose-dependent paralytic effects and minimal diffusion effects on surrounding musculature . It has been suggested that conversion of Botox and Xeomin doses can be performed in a 1:1 ratio allowing exchange of both BTX drugs in a therapeutic setting.

Prosigne (Lanzhou Biological Products Institute, China) is a BTX-A that is only approved in China; it has been available for clinical use there since October 1993 . Preliminary studies suggest that Prosigne may have therapeutic actions comparable with Botox for some therapeutic purposes . Trials specifically examining Prosigne for cosmetic uses are lacking .

PurTox (Mentor Corp, Santa Barbara, CA, USA) is a purified BTX-A that is undergoing trials to approve its efficacy in some therapeutic uses .

BTX-B

BTX-B is available as Myobloc (Solstice Pharmaceuticals, South San Francisco, CA, USA) and is marketed as Neurobloc (Elan Pharmaceuticals, Shannon, County Clare, Ireland) . Myobloc has shown efficacy in clinical trials for the treatment of various movement disorders since 1995 and was approved by the FDA for the treatment of cervical dystonia and hemifacial spasm in 2001 . Myobloc has not received cosmetic approval in any country, but there are reports of its efficacy in the treatment of lateral canthal, glabellar and forehead rhytides. It appears to offer versatility in cosmetic neuroblockade by exhibiting action in patients resistant to BTX-A products .

Myobloc is preconstituted in vials containing 25 ng (2500 U)/0.5 cc, 50 ng (5000 U)/1.0 cc and 100 ng (10,000 U)/2.0 cc of product in solution with 0.05% albumin . Treatment of patients with cervical dystonia with Botox and Myobloc led to attempts at equivalency doses in many cosmetic studies (1 U Botox equals approximately 50–100 U Myobloc), but the optimal ratio has not been established .

Studies comparing the cosmetic efficacies of BTX-A and BTX-B report that the latter causes more pain during injection, has shorter action and probably a less predictable diffusion pattern . BTX-B could be useful in situations in which rapid onset is desirable or in which there are concerns about antibody production to BTX-A .

Cosmetic Uses

Intramuscular injection of BTX to reduce facial wrinkles is the most common cosmetic procedure performed in many countries. In conjunction with fillers, BTXs allow the practitioner to sculpt the face through alterations in the dynamics of the facial muscles. The limited on-label uses of these drugs for hyperkinetic forehead wrinkles and brow furrows belie its range of cosmetic applications.

Facial Wrinkles

Glabellar lines, also called frown lines, occur naturally with facial animation, as a result of the pulling of the skin by the underlying musculature, predominantly the procerus muscle and the corrugator supercilii. With aging and chronic activity of the facial muscles, these lines become more prominent . The cosmetic potential of BTX-A was first explored in the mid 1980s in the treatment of hyperfunctional facial lines. Since then, BTX-A has been used to temporarily treat glabellar lines and other hyperfunctional facial lines such as horizontal forehead lines, lateral canthal lines ‘crow’s feet’, platysma bands and perioral lines . The evidence for the effect of BTX in the treatment of facial wrinkles is level 2 evidence (evidence from randomized controlled trials).

The technique for injecting BTX is generally simple and most patients tolerate injections without anesthesia quite well, although topical anesthetics are used by some practitioners. Some have used acid mantle cream mixed with lidocaine (4%) and Lidoderm patches (lidocaine 5%) . Many patients treated with topical anesthesia elected not to use it for subsequent treatments .

Multiple injection techniques have been described. Some authors describe a method based on brow position . Others describe a method based on needle angulation and measurement . All injections are now made perpendicular to the skin surface and are tailored to the specific anatomy, but they must be 10 mm away from the bony orbit because the apparent diffusion of BTA is approximately 10 mm .

Botox has only been approved officially for the treatment of glabellar lines, but other uses have shown the same degree of improvement for frontalis and lateral canthal regions. Botox has also been used for the reduction of platysmal bands . Several patients with mentalis wrinkling and lower eyelid orbicularis hypertrophy were treated successfully with Botox injections . Other sites treated include the vertical lip rhytids (lipstick lines) with minimal improvement and good patient satisfaction but perioral muscular palsy was reported in some cases . Some have described an improvement in patients with excessive gingival exposure. By weakening the lip elevators, the amount of movement decreases and the patient shows less gingiva on smiling .

Masseteric and temporalis muscle hypertrophy

Masseteric hypertrophy usually results from anatomical asymmetry of the jaw, habitual asymmetric use of the jaw, clenching during exercise or sleep, excessive chewing of gum or congenital malformations. It may be unilateral or bilateral. The early results of treatment with intramasseter injections of BTX have been encouraging and satisfying to patients, but the effect has not been well quantified .

Temporalis muscle hypertrophy is less common but has been managed successfully using BTX injection; there were no appreciable side effects .

Therapeutic Uses

BTX has evolved from a poison to a versatile clinical tool for a growing list of conditions resulting from muscular hyperfunction. In the head and neck, this list includes focal dystonias, vocal tics and stuttering, cricopharyngeal achalasia, various manifestations of tremor, hemifacial spasm, temporomandibular joint dysfunction, bruxism, masticatory myalgias, sialorrhea, hyperhidrosis and headache . Recently, it has been reported for clinical use in dental implantology for the prophylactic reduction of masseter and temporalis muscle strength after implantation in immediate load protocols .

Temporomandibular joint (TMJ)

Many reports on BTX-A treatment for TMJ disorders have dealt with TMJ and masticatory muscle pain , reduced jaw opening capacity , recurrent TMJ dislocations , and masticatory hyperactivity . Most of these studies were case series (level 4 evidence).

Temporomandibular disorders (TMDs) are subgroups of musculoskeletal and rheumatologic disorders, and are considered the major cause of pain in the orofacial region . TMDs may be divided into those related to the muscles acting on the joint (myofascial) and those related to the joint itself (arthrogenic). Joint noise, pain and a restricted range of mandibular motion are the most frequent symptoms of TMD . Directing treatment at the muscular component of TMD, which in some patients can be identified as non-spastic clenching or bruxism, could yield important therapeutic gains. BTX-A has been effective in the treatment of some patients with TMD with high specificity as well as tolerable side-effects . Injections are usually performed under electromyographic or ultrasonic control .

The source of chronic myofascial pain is not clear . There is some consensus that peripheral and central mechanisms are variably involved in the propagation of pain in TMD . The injection of BTX-A into the masseter and temporalis muscles of patients with TMD reduced subjective pain and tenderness in some patients coincident with the objective and subjective weakening of the masticatory muscles and not before . This observation was attributed to the presumed action of BTX on nociceptors and the inhibitory effect of specific protein-receptor binding within the intracellular compartment on the release of neuropeptides and inflammatory molecules, such as calcitonin gene-related peptide, substance P, and glutamate .

Most patients with restricted mouth opening experienced some degree of improvement in the maximal range of vertical motion after BTX therapy. Muscular relaxation, reduction of inflammation in the muscle and the TMJ, and the guarding response to pain may contribute to this finding .

Earlier studies suggest that displacement of the articular disc may be caused, precipitated or maintained by lateral pterygoid activity or friction between the articular surfaces of the disc and condyle causing clicking . BTX injection into the lateral pterygoid muscle has reduced the clicking associated with TMD . Clicking was permanently eliminated in some cases with a small but distinctive positional improvement in the disc–condyle relationship .

The term ‘bruxism’ is derived from the Greek word brychein , which means ‘to grind or gnash the teeth’ . When severe, this rhythmic grinding is associated with headache, masseter hypertrophy, dysarthria, TMJ destruction and dental wear . Several studies have described the treatment of bruxism with BTX . Some authors have found that BTX-A injection into the flexor muscles of the mandible produced subjective and objective reductions in the power of muscular voluntary contraction in most subjects . There have been no double-blind studies to assess the effectiveness of BTX therapy in bruxism.

Arthrocentesis is a less invasive surgical intervention than open arthrotomy to relieve the discomfort and dysfunction associated with chronic cases of internal derangement of TMJ . Intramuscular injection of BTX as an adjunct to arthrocentesis of the TMJ gave encouraging results regarding duration of improvement, suggesting that there may be synergy between the two procedures .

Dislocation of the TMJ occurs when the mandibular condyle is displaced anteriorly beyond the articular eminence. It represents 3% of all reported dislocated joints . There have been several anecdotal reports of the use of BTX-A as treatment for TMJ dislocation , but a controlled clinical trial is needed to prove evidence of its efficacy. BTX-A was first used to treat surgical failures and then used as initial treatment . The muscle selected varies with each case, but the lateral pterygoid is that most commonly reported. Treating only the lateral pterygoid muscle appears to be sufficient to prevent temporarily recurrent dislocation of the TMJ , but, in some reports, the superficial part of the masseter at the angle of the mandible was also injected .

BTX injection is invasive, but it is a relatively conservative option. It is specifically indicated in patients for whom conservative treatment of recurrent dislocation of the TMJ has failed and for whom surgery carries major risks. BTX injection therapy is also an option in patients who suffer recurrent dislocation of the TMJ as a result of impaired muscle coordination secondary to oromandibular dystonia, neuroleptically induced early and late dyskinesias, epilepsy and brain-stem syndromes .

BTX treatment of protracted TMJ dislocation after medical conditions such as anoxic encephalopathy and stroke or cerebrovascular event has also been reported, which could lead to an increase in verbalization, mastication and improved quality of life.

Salivary secretory disorders

Xerostomia is one of the first manifestations of botulism, which led to investigations of its application for sialorrhea and drooling. Topical injection of BTX-A as a minimally invasive option for the treatment of drooling has been used for many years in neurological diseases . Its greatest limitation in this indication is its transient effectiveness (3–4 months), requiring multiple and expensive administrations . The therapeutic effect is based on the inhibitory action of the toxin at the cholinergic receptors of the salivary gland cells, shown in animal experiments . An initial animal model showed a significant reduction in saliva production without direct toxicity to the acinar cells .

Only pilot studies with relatively small groups of patients are available with a brief follow-up (level 4 evidence), although here are some studies on sialorrhea associated with Parkinson’s disease [level 2 evidence (randomized clinical trials)]. The outcome of using BTX-A in the treatment of drooling appears to be uniformly favorable; the preliminary results are promising, with rare reports of serious complications. Up to two-thirds of patients experienced a marked or moderate improvement in drooling after the treatment of both parotid glands or parotid and submandibular glands combined . Treatment is mostly focused on the parotid gland and to a lesser extent on the submandibular gland. The sublingual gland is seldom injected .

BTX has found application for sialorrhea in Parkinson’s disease , amyotrophic lateral sclerosis , cerebral palsy , and carcinoma of the upper digestive tract. It has also been used for accumulated saliva and drooling caused by swallowing disorders after tumor operations of the upper aerodigestive tract and for diseases of the glandular tissue such as posttraumatic and iatrogenic salivary sialoceles and cysts or salivary fistulas after sialadenectomy or oropharyngeal cancer surgery where the temporary stopping of glandular secretory action is needed to promote healing. It has also been used successfully to treat auriculotemporal (Frey’s) syndrome as it reduces the skin area affected by gustatory sweating by inhibiting the sweat glands abnormally re-innervated by the cholinergic pathway . BTX-A also has advantages in temporarily drooling states because its effect is only temporary . In patients with recurrent and chronic parotitis, BTX injection resulted in a reduction in the number of episodes of parotid swelling . BTX-B has also been successful in some cases .

With the exception of those with Frey’s syndrome who are treated intracutaneously, all of the injections are performed percutaneously, either intraparenchymal or perilesional. In the case of sialoceles, the extravasation fluid should be drained beforehand . Some authors still use BTX injections under EMG control when treating salivary secretory disorders. According to others, ultrasonographic-assisted intraparenchymal infiltration is preferable and improves efficacy and safety . Others have found no difference in undesired effects associated with the method of drug application .

Facial pain (other than myofascial origin)

Chronic facial pain often presents difficult management problems requiring interdisciplinary consultations and multiple attempts with different therapies. BTX injections showed some advantages over existing therapies regarding safety and efficacy . The evidence provided by the literature in this area lies in level 2 (randomized clinical trials).

Facial pain relief has been reported after treatment by BTX for other reasons; such conditions include regional dystonias , facial wrinkles , and skull base surgery . These observations led to the study of non-dystonic pain syndromes, such as myofascial pain and tension headache, these produced beneficial results and were then studied in larger controlled trials . Several studies have been conducted on the use of BTX-A in pain conditions such as tension headache, myofascial pain, migraine, trigeminal neuralgia, bruxism and hemifacial contracture after seventh cranial nerve injury . BTX-A was found promising in postoperative wound pain including reconstructive facial and oral surgery, traditional and endoscopic sinus surgery, TMJ surgery and blowout fracture repair . Chronic facial pain following post-dental procedures was associated with a poor results .

Similar benefits have been reported with the use of BTX-B . The ultimate efficacy of BTX in pain is difficult to assess and the data available do not permit definitive conclusions. Other studies did not show a beneficial effect of BTX-A .

Facial nerve palsy (FNP)

FNP is a disfiguring condition, different aspects of which have been treated successfully using BTX. Most studies were case series (level 4 evidence).

BTX injection, through an orbital route or a skin crease, provides a good means of inducing a protective ptosis by temporarily paralyzing the levator palpebrae superioris . This intentionally induced ptosis may be useful in intensive care patients to prevent desiccation of the cornea .

Synkinesis is an involuntary uncoordinated muscle movement associated with voluntary movement of the muscle. It is secondary to aberrant regeneration . BTX-A is commonly used to relieve the symptoms of synkinesis with marked improvement .

In patients with facial asymmetry, chemo-denervation of the normal side with BTX has been reported to be an effective disguising tool. In this setting, BTX reduces the relative hyperkinesis of the contralateral side to the paralysis, resulting in a more symmetrical function of the face.

An aberrant connection of the salivary sceromotor fibres to the fibres of the lacrimal gland may develop after a facial palsy, causing a hyperlacrimation whenever the patient salivates (crocodile tears). Injection of BTX into the lacrimal gland is a successful treatment for hyperlacrimation in these cases .

Other nerve palsies

Trauma is a common cause of acquired third-nerve palsy in adults and children . Such patients are less likely to recover than those with palsies of other causes . There are few reports (level 4 evidence) of BTX injection to the lateral rectus muscle for treatment of third-nerve palsy . BTX injection decreases the likelihood of contracture of the lateral rectus muscle, thereby allowing return of medial rectus muscle function .

The abducens nerve can be injured during a severe orbital trauma . In such cases, BTX injection of the medial rectus muscle has been studied with variable improvements .

Muscle movement disorders

BTX has been used since 1977 as a therapeutic agent in the treatment of numerous neuromuscular disorders . BTX-A injections are considered a safe and efficient local treatment for focal dystonia and muscle spasms . Other serotypes have been used with comparable effects .

Dystonia refers to the involuntary contraction of specific muscles. Numerous studies document the usefulness of BTX therapy in the treatment of oromandibular dystonia , cervical dystonia (spasmodic torticollis) , hemifacial spasm , tardive dyskinesia , and tardive tongue protrusion dystona . Many studies were double-blind randomized trials (level 2 evidence).

A specific type in this category is hyperkinesia of the platysma. In the literature, data on successful treatment of the platysma with BTX are nearly always related to its use for aesthetic indications . BTX also provides a favorable therapeutic option .

Perioperative use of botulinum toxins

In patients with movement disorders who require surgery, the presence of postoperative involuntary movements may be detrimental to healing. BTX weakens the muscle and in so doing may improve postoperative recovery and healing. Wound healing improves if the muscles involved are injected with BTX prior to surgery .

In maxillofacial surgery, patients undergoing eyelid reconstructive surgery had successful wound healing after adjunct treatment with BTX . BTX was better than placebo in the wound healing of facial lacerations requiring surgery . BTA has been used to immobilize muscles after jaw fractures (level 4 evidence) to reduce the displacing forces on the fracture ends and obtain good immobilization especially if rigid internal fixation is not available or feasible.

BTX has also been beneficial during the initial osseointegration phase for dental implants. This indication is mostly experimental, but some authors have found it to be safe and effective in the prophylactic reduction of masseter and temporalis muscle strength after implantation in immediate loading protocols .

Complications

Botox has a large margin of safety . The most important side effects reported for cosmetic use of BTX include immunogenicity, allergy and local complications.

Neutralizing antibodies to BTX-A toxins can lead to loss of treatment effect. Clinical resistance to BTX-A has been estimated as high as 7% , and BTX-B is being investigated as an alternative therapeutic agent .

In theory, because human albumin is used in the preparation of Botox, a patient could exhibit an allergic reaction, but no case has been reported.

Adverse effects such as pain, oedema, erythema, ecchymosis and short-term hypoesthesia may occur after injection of BTX-A . Other reported adverse events are headache, blepharoptosis and perioral muscular palsy .

In therapeutic applications, complications were mostly local and relatively mild, such as pain, erythema, ecchymosis of the region injected, dry eyes, mouth droop, ptosis and lid edema, facial muscle weakness, asymmetry of facial expression during dynamic facial movements, xerostomia, transient dysphagia, restricted mouth opening, nasal regurgitation and nasal speech, headache, blurred vision, dizziness, upset stomach, infection, neck weakness, voice changes, difficulties in chewing and breathing risk of aspiration, recurrent jaw dislocation, dysarthria, salivary duct calculi and local injuries of the carotid arteries or branches of the facial nerve .

Systemic side effects are rarely reported, generally not dose related, and can include transient weakness, fatigue, nausea and pruritis . Flu-like syndromes have been reported, but they are generally of brief duration .

Some adverse effects such as xerostomia and dysphagia are more frequently seen after treatment with BTX-B than BTX-A .

Contraindications

Contraindications to BTX-A are generally few. In many studies, no complaints were received about systemic problems associated with cosmetic injection. Allergan lists Botox contraindications as pregnancy and breastfeeding, disorders of the neuromuscular junction (myasthenia gravis, amyotrophic lateralizing sclerosis, myopathies) and theoretical drug interactions (aminoglycoside antibiotics, quinidine, calcium channel blockers, magnesium sulfate, succinylcholine, and polymyxin) . Other reported contraindications are Eaton–Lambert syndrome and hypersensitivity to BTX or one of its ingredients .

Potential Therapeutic Uses

Topical Formulations

Because intradermal BTX injection has been successful in treating focal hyperhidrosis of the palms, soles, axillae and facial areas , investigators have considered the potential for a topical formulation. Topical BTX has been used for axillary hyperhidrosis with promising results .

Keloid and Hypertrophic Scar

Clinical observations indicate that BTX-A can improve the appearance of hypertrophic scar and inhibit its growth . Evidence supporting this potential use arise from BTX’s ability to prevent excessive muscle contraction of the skin near keloid tissue , and its reported influence on cellular apoptosis and cellular proliferation .

Funding

None.

Competing interests

None declared.

Ethical approval

Not required.

References

  1. 1. Acquadro M., and Borodic G.E.: Treatment of myofascial pain with botulinum toxin. Anesthesiology 1994; 80: pp. 705-706
  2. 2. A C. Perioperative Use Of Botulinum Toxins. Abstracts Toxins 2008; Toxicon : 44.
  3. 3. Alster T., and Lupton J.: Botulinum toxin type B for dynamic glabellar rhytides refractory to botulinum toxin type A. Dermatol Surg 2003; 29: pp. 516-518
  4. 4. A M, G P: Efficacy and safety of Myobloc in headache prophylaxis: A retrospective observation. Abstracts Toxins 2008/Toxicon 51: p. 44.
  5. 5. Aoki K.R., and Guyer B.: Botulinum toxin type A and other botulinum toxin serotypes: a comparative review of biochemical and pharmacological actions. Eur J Neurol. 2001; 8: pp. 21-29
  6. 6. Aquilina P., Vickers R., and Mckellar G.: Reduction of a chronic bilateral temporomandibular joint dislocation with intermaxillary fixation and botulinum toxin A. Br J Oral and Maxillofac Surg 2004; 42: pp. 272-273
  7. 7. Armstrong M.W., Mountain R.E., and Murray J.A.: Treatment of facial synkinesis and facial asymmetry with botulinum toxin type A following facial nerve palsy. Clin Otolaryngol Allied Sci 1996; 21: pp. 15-20
  8. 8. Arnaud S., Batifor D., and Goudot P.: Nonsurgical management of traumatic injuries of the parotid gland and duct using type A botulinum toxin. Plast Reconstr Surg 2006; 117: pp. 2426-2430
  9. 9. Bakke M., Møller E., Werdelin L.M., Dalager T., and Kitai N.: Treatment of severe temporomandibular joint clicking with botulinum toxin in the lateral pterygoid muscle in two cases of anterior disc displacement. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005; 100: pp. 693-700
  10. 10. Bakke M., Werdelin L.M., Dalager T., Fuglsang-Frederiksen A., Prytz S., and Møller E.: Reduced jaw opening from paradoxical activity of mandibular elevator muscles treated with botulinum toxin. Eur J Neurol 2003; 10: pp. 695-699
  11. 11. Baumann L., Stezinger A., Vujevich J., Halem M., Bryde J., and Black L.: A double-blinded, randomized, placebo-controlled pilot study of the safety and efficacy of Myobloc (botulinum toxin type B)-purified neurotoxin complex for the treatment of crow’s feet: A double-blinded, placebo- controlled trial. Dermatol Surg 2003; 29: pp. 508-515
  12. 12. Bentsianov B., Francis A., and Blitzer A.: Botulinum toxin treatment of temporomandibular disorders, masseteric hypertrophy, and cosmetic masseter reduction. Oper Tech Otolaryngol Head Neck Surg 2004; 15: pp. 110-113
  13. 13. Blitzer A, Binder W.J., and Aviv J.E.: The management of hyperfunctional facial lines with botulinum toxin: A collaborative study of 210 injection sites in 162 patients. Arch Otolaryngol Head Neck Surg 1997; 123: pp. 389-392
  14. 14. Blitzer A., Brin M.F., Greene P.E., and Fahn S.: Botulinum toxin injection for the treatment of oromandibular dystonia. Ann Otol Rhinol Laryngol 1989; 98: pp. 93-97
  15. 15. Blitzer A., and Sulica L.: Botulinum toxin: basic science and clinical uses in otolaryngology. Laryngoscope 2001; 111: pp. 218-226
  16. 16. Boghen D., and Flanders M.: Effectiveness of botulinum toxin in the treatment of spasmodic torticollis. Eur Neurol 1993; 33: pp. 199-203
  17. 17. Borodic G., and Acquadro M.: Management of facial pain with botulinum toxin in a tertiary pain clinic. Naunyn Schmiedebergs Arch Phannacol 2002; 365: pp. R14
  18. 18. Borodic G.E., and Acquadro M.A.: The Use of Botulinum Toxin for the Treatment of Chronic Facial Pain. J Pain 2002; 3: pp. 21-27
  19. 19. Borodic G.E., Pearce L.B., and Cheney M.: Botulinum A toxin for treatment of aberrant facial nerve regeneration. Plast Reconstr Surg 1993; 91: pp. 1042-1045
  20. 20. B P I . Irvine, CA, Allergan, Inc.
  21. 21. Brandt F.S., and Bellman B.: Cosmetic use of botulinum toxin Aexotoxin for the aging neck. Dermatol Surg 1998; 24: pp. 1232-1234
  22. 22. Brashear A., Lew M.F., Dykstra D.D., Comella C.L., Factor S.A., and Rodnitzky R.L.: Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-responsive cervical dystonia. Neurology 1999; 53: pp. 1439-1446
  23. 23. Brin M.F.: Botulinum toxin therapy: basic science and overview of other therapeutic applications. In Blitzer A. (eds): Management of facial lines and wrinkles. Philadelphia: Lippincott, Williams and Wilkins, 2000 p. pp. 279-302
  24. 24. Brin M.F., Blitzer A., and Herman S.: Orofaciomandibular and lingual dystonia. In Moore A.P. (eds): Handbook of Botulinim Toxin Treatment. Oxford, England: Blackwell Scientific, 1995. pp. 151-163
  25. 25. Brin M.F., Blitzer A., and Herman S.: Oromandibular dystonia: Treatment of 96 patients with botulinum toxin. In Jankovic J., and Hallett M. (eds): Therapy With Botulinum Toxin.. New York, NY: Marcel Dekker, 1994. pp. 429-435
  26. 26. Brin M.F., Fahn S., and Moskowitz C.: Localized injections of botulinum toxin for the treatment of focal dystonias and hemifacial spasm. Mov Disord 1987; 2: pp. 237-254
  27. 27. Brin M.F., Lew M.F., Adler C.H., Comella C.L., Factor S.A., and Jankovic J.: Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-resistant cervical dystonia. Neurology 1999; 53: pp. 1431-1438
  28. 28. Bulstrode N.W., and Harrison D.H.: The phenomenon of the late recovered Bell’s palsy: treatment options to improve facial symmetry. Plast Reconstr Surg 2005; 115: pp. 1466-1471
  29. 29. Bushara K.O.: Sialorrhea in amyotrophic lateral sclerosis: a hypothesis of a new treatment-botulinum toxin A injections of the parotid glands. Med Hypotheses 1997; 48: pp. 337-339
  30. 30. Capaccio P., Cuccarini V., and Benicchio V.: Treatment of iatrogenic submandibular sialocele with botulinum toxin. Case report. Br J Oral Maxillofac Surg 2007; 45: pp. 415-417
  31. 31. Capaccio P., Paglia M., Minorati D., et al: Diagnosis and therapeutic management of iatrogenic parotid sialocele. Ann Otol Rhinol Laryngol 2004; 113: pp. 562-564
  32. 32. Capaccio P., Torretta S., Osio M., and Minorati D.: Botulinum toxin therapy: a tempting tool in the management of salivary secretory disorders. Am J Otol – Head and Neck Medicine and Surgery 2008; 29: pp. 333-338
  33. 33. Carruthers A., and Carruthers J.: Botulinum toxin type A: History and current cosmetic use in the upper face. Semin Cutan Med Surg 2001; 20: pp. 71-84
  34. 34. C A: Facial aesthetic enhancement educational initiative. Chicago, IL, Faculty Training, July 2001; 13-15.
  35. 35. Carruthers J., and Carruthers A.: The evolution of botulinum neurotoxin type A for cosmetic applications. J Cosmet Laser Ther 2007; 9: pp. 186-193
  36. 36. Carruthers J., and Carruthers A.: Treatment of glabellar frown lines with C. botulinum-A exotoxin. J Dermatol Surg Oncol 1992; 18: pp. 17-21
  37. 37. Carruthers J.A., Lowe N.J., Menter M.A., Gibson J., Nordquist M., and Mordaunt J.: A multicenter, double-blind, randomized, placebo-controlled study of the efficacy and safety of botulinum toxin type A in the treatment of glabellar lines. J Am Acad Dermatol 2002; 46: pp. 840-849
  38. 38. Carruthers S.J., Fagien S., and Matarasso S.L.: Consensus recommendations on the use of botulinum toxin type A in facial aesthetics. Plast Reconstr Surg 2004; 114: pp. 1S-22S
  39. 39. Cather J.C., Cather J.C., and Menter A.: Update on botulinum toxin for facial aesthetics. Dermatol Clin 2002; 20: pp. 749-761
  40. 40. Charles P.D., Davis T.L., Shannon K.M., Hook M.A., and Warner J.S.: Tongue protrusion dystonia: treatment with botulinum toxin. South Med J 1997; 90: pp. 522-525
  41. 41. Cherington M.: Botulism: update and review. Semin Neurol 2004; 24: pp. 155-163
  42. 42. Chua C.N., Quhill F., and Jones E.: Treatment of aberrant facial nerve regeneration with botulinum toxin A. Orbit 2004; 23: pp. 213-218
  43. 43. Clark R.P., and Berris C.E.: Botulinum toxin: a treatment for facial asymmetry caused by facial nerve paralysis. Plast Reconstr Surg 2005; 115: pp. 573-574
  44. 44. Comella C.L., Jankovic J., Shannon K.M., Tsui J., Swenson M., and Leurgans S.: Comparison of botulinum toxin serotypes A and B for the treatment of cervical dystonia. Neurology 2005; 65: pp. 1423-1429
  45. 45. Daelen B., Thorwirth V., and Koch A.: Treatment of recurrent dislocation of the temporomandibular joint with type A botulinum toxin. Int J Oral Maxillofac Surg 1997; 26: pp. 458-460
  46. 46. David A., Sherris M., and Holger G.: Botulinum toxin to minimize facial scarring. Facial Plast Surg 2002; 18: pp. 35-39
  47. 47. De Almeida A.T., Marques E., De Almeida J., Cunha T., and Boraso R.: Pilot study comparing the diffusion of two formulations of botulinum toxin type A in patients with forehead hyperhidrosis. Dermatol Surg 2007; 33: pp. S37-S43
  48. 48. De Bont L.G., and Stegenga B.: Pathology of temporomandibular joint internal derangement and osteoarthrosis. Int J Oral Maxillofac Surg 1993; 22: pp. 71-74
  49. 49. De Paiva A., Meunier F.A., Molgo J., Aoki K.R., and Dolly J.O.: Functional repair of motor endplates after botulinum neurotoxin type Apoisoning: biphasic switch of synaptic activity between nerve sprouts and their parent terminals. Proc Natl Acad Sci U S A 1999; 96: pp. 3200-3205
  50. 50. Dembek Z.F., Smith L.A., and Rusnak J.M.: Botulinum Toxin (chapter 16). In Dembek Z.F. (eds): Medical Aspects of Biological Warfare. Virginia: Office of The Surgeon General, 2007. pp. 337-353
  51. 51. Dogu O., Apaydin D., Sevim S., Talas D.U., and Aral M.: Ultrasoundguided versus blind intraparotid injections of botulinum toxin- A for the treatment of sialorrhoea in patients with Parkinson’s disease. Clin Neurol Neurosurg 2004; 106: pp. 93-96
  52. 52. Dressler D., and Benecke R.: Autonomic side effects of botulinum toxin type B treatment of cervical dystonia and hyperhidrosis. Eur Neurol. 2003; 49: pp. 34-38
  53. 53. D D, M GJ, F K. Equivalent potency of Xeomin and BOTOX. Abstracts Toxins 2008/Toxicon 51: 10.
  54. 54. Drobik C., and Laskawi R.: Frey’s syndrome: treatment with botulinum toxin. Acta Otolaryngol Stockh 1995; 115: pp. 459-461
  55. 55. Drummond P.: Mechanism of gustatory flushing in Frey’s syndrome. Clin Auton Res 2002; 12: pp. 144-146
  56. 56. Durham P.L., Cady R., and Cady R.: Regulation of calcitonin gene-related peptide secretion from trigeminal nerve cells by botulinum toxin type A: implications for migraine therapy. Headache 2004; 44: pp. 35-42
  57. 57. Dworkin S.F.: A model for pain mechanisms in myogenous temporomandibular disorders. Pain Forum 1997; 6: pp. 166-169
  58. 58. Dworkin S.F., and Leresche L.: Research diagnostic criteria for temporomandibular disorders: Review, criteria, examinations and specifications, critique. J Craniomandib Disord Facial Oral Pain 6:301-55 1992; undefined:
  59. 59. Ellies M., Gottstein U., and Rohrbach-Volland S.: Reduction of salivary flow with botulinum toxin: extended report on 33 patients with drooling, salivary fistulas, and sialadenitis. Laryngoscope 2004; 114: pp. 1856-1860
  60. 60. Ellies M., Laskawi R., and Gotz W.: Immunohistochemical and morphometric investigations of the influence of botulinum toxin on the submandibular gland of the rat. Eur Arch Otorhinolaryngol 1999; 256: pp. 148-152
  61. 61. Ellies M., Laskawi R., Rohrbach-Volland S., and Arglebe C.: Up-todate report of botulinum toxin therapy in patients with drooling caused by different etiologies. J Oral Maxillofac Surg 2003; 61: pp. 454-457
  62. 62. Ellies M., Laskawi R., and Rohrbach-Volland S.: Botulinum toxin to reduce saliva flow: Selected indications for ultrasound guided toxin application into salivary glands. Laryngoscope 2002; 112: pp. 82-86
  63. 63. Ellies M., Laskawi R., and Tormahlen G.: The effect of local injection of botulinum toxin A on the parotid gland of the rat: An immunohistochemical and morphometric study. J Oral Maxillofac Surg 2000; 58: pp. 1251-1256
  64. 64. Ellis M.F., and Daniell M.: An evaluation of the safety and efficacy of botulinum toxin type A (BOTOX) when used to produce a protective ptosis. Clin Exp Ophthalmol 2001; 29: pp. 394-399
  65. 65. Elston J.S.: Botulinum toxin A in clinical medicine. J Physiol (Paris) 1990; 84: pp. 285-289
  66. 66. Erbguth F.J., and Naumann M.: Historical aspects of botulinum toxin: Justinus Kerner (1786–1862) and the “sausage poison”. Neurology 1999; 53: pp. 1850-1853
  67. 67. Evers S., Vollmer-Haase J., Schwaag S., Rahmann A., Husstedt I.W., and Frese A.: Botulinum toxin A in the prophylactic treatment of migraine—a randomized, double-blind, placebo-controlled study. Cephalalgia 2004; 24: pp. 838-843
  68. 68. Fagien S., and Brandt F.S.: Primary and adjunctive use of botulinum toxin type A (Botox) in facial aesthetic surgery: beyond the glabella. Clin Plast Surg 2001; 28: pp. 127-148
  69. 69. Fagien S., Cox S.E., Finn J.C., Werschler W.P., and Kowalski J.W.: Patient-reported outcomes with botulinum toxin type A treatment of glabellar rhytids: A double-blind, randomized, placebo-controlled study. Dermatol Surg 2007; 33: pp. S2-S9
  70. 70. Flynn T.C.: Myobloc. Dermatol Clin 2004; 22: pp. 207-211
  71. 71. Flynn T.C.: Update on botulinum toxin. Semin Cutan Med Surg 2006; 25: pp. 115-121
  72. 72. Flynn T.C., Carruthers J., and Carruthers A.: Botulinum-A toxin treatment of the lower eyelid improves infraorbital rhytides and widens the eye. Dermatol Surg 2001; 27: pp. 703-708
  73. 73. Flynn T.C., and Clark R.E.: Botulinum toxin type B (MYOBLOC) versus botulinum toxin type A (BOTOX) frontalis study: rate of onset and radius of diffusion. Dermatol Surg 2003; 29: pp. 519-522
  74. 74. Foran P., Mohammed N., and Lisk G.: Evaluation of the therapeutic usefulness of botulinum neurotoxins B, C1, E, and F compared with the long lasting type A. Basis for distinct durations of inhibition of exocytosis in central neurons. J Biol Chem. 2003; 278: pp. 1363-1371
  75. 75. Frampton J.E., and Easthope S.E.: Botulinum toxin A (Botox cosmetic): a review of its use in the treatment of glabellar frown lines. Am J Clin Dermatol 2003; 4: pp. 709-725
  76. 76. Franz D.R., Pitt L.M., Clayton M.A., Hanes M.A., and Rose K.J.: Efficacy of prophylactic and therapeutic administration of antitoxin for inhalation botulism. In DasGupta B.R. (eds): Botulinum and Tetanus Neurotoxins: Neurotransmission and Biomedical Aspects. New York, NY: Plenum Press, 1993. pp. 473-476
  77. 77. Freeman S.R., and Cohen J.L.: New Neurotoxins on the Horizon. Aesthetic Surg J 2008; 28: pp. 325-330
  78. 78. Freund B., and Schwartz M.: Intramuscular injection of botulinum toxin as an adjunct to arthrocentesis of the temporomandibular joint: preliminary observations. Br J Oral Maxillofac Surg 2003; 41: pp. 351-352
  79. 79. Freund B., and Schwartz M.: Temporal relationship of muscle weakness and pain reduction in subjects treated with botulinum toxin A. J Pain 2003; 4: pp. 159-165
  80. 80. Freund B., Schwartz M., and Symington J.M.: Botulinum toxin: new treatment for temporomandibular disorders. Br J Oral and Maxillofac Surg 2000; 38: pp. 466-471
  81. 81. Freund B., Schwartz M., and Symington J.M.: The Use of Botulinum Toxin for the Treatment of Temporomandibular Disorders: Preliminary Findings. J Oral Maxillofac Surg 1999; 57: pp. 916-920
  82. 82. Freund B.J., and Schwartz M.: The use of botulinum toxin for the treatment of temporomandibular disorder. Oral Health 1998; 88: pp. 32-37
  83. 83. Freund B.J., and Schwartz M.: Relief of tension-type headache symptoms in subjects with temporomandibular disorders treated with botulinum toxin-A. Headache 2002; 42: pp. 1033-1037
  84. 84. Freund B.J., and Schwartz M.: Treatment of chronic cervical-associated headache with botulinum toxin A: A pilot study. Headache 2000; 40: pp. 231-236
  85. 85. Frost De , and Kendell B.D.: Part II. The use of arthrocentesis for treatment of temporomandibular joint disorders. J Oral Maxillofac Surg 1999; 57: pp. 583-587
  86. 86. Giess R., Naumann M., and Werner E.: Injections of botulinum toxin A into the salivary glands improve sialorrhoea in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 2000; 69: pp. 121-123
  87. 87. Gill D.M.: Bacterial toxins: a table of lethal amounts. Microbiol Rev. 1982; 46: pp. 86-94
  88. 88. Glogau R.G.: Topically applied botulinum toxin type A for the treatment of primary axillary hyperhidrosis: Results of a randomized, blinded, vehicle-controlled study. Dermatol Surg 2007; 33: pp. S76-S80
  89. 89. Gusek-Schneider G.C., and Erbguth F.: Protective ptosis by botulinum A toxin injection in corneal affectations. Klin Monatsbl Augenheilkd 1998; 213: pp. 15-22
  90. 90. Hallett M.: One man’s poison—Clinical applications of botulinum toxin. N Engl J Med 1999; 341: pp. 118-120
  91. 91. Halpern J.L., Smith L.A., Seamon K.B., Groover K.A., and Habig W.H.: Sequence homology between tetanus and botulinum toxins detected by an antipeptide antibody. Infect Immun. 1989; 57: pp. 18-22
  92. 92. Hatheway C.L.: Clostridium botulinum and other clostridia that produce botulinum neurotoxins. In Hauschild A.H.W., and Dodds K.L. (eds): Clostridium botulinum—Ecology and Control in Foods. New York, NY: Marcel Dekker, Inc, 1992. pp. 3-10
  93. 93. Hegedus F., Diecidue R., Taub D., and Nyirady J.: Non-surgical treatment modalities of facial photodamage: practical knowledge for the oral and maxillofacial professional. Int. J. Oral Maxillofac. Surg. 2006; 35: pp. 389-398
  94. 94. Hennings J.M.H., Krause E., Bötzel K., and Wetter T.C.: Successful treatment of tardive lingual dystonia with botulinum toxin: Case report and review of the literature. Progress in Neuro-Psychopharmacology & Biological Psychiatry 2008; 32: pp. 1167-1171
  95. 95. Hermanowicz N., and Truong D.D.: Treatment of oromandibular dystonia with botulinum toxin. Laryngoscope 1991; 101: pp. 1216-1218
  96. 96. Herrero B.A., Ecklung A.E., Streett C.S., Ford D.F., and King J.K.: Experimental botulism in monkeys—Aclinical pathological study. Exp Mol Pathol. 1967; 6: pp. 84-95
  97. 97. Hofmann R.J.: Treatment of Frey’s syndrome (gustatory sweating) and ‘crocodile tears’ (gustatory epiphora) with purified botulinum toxin. Ophthalmic Plast Reconstr Surg 2000; 16: pp. 289-291
  98. 98. Hogan P., Charles D., Watts M.W., and Massey J.M.: Severity and Impact of Xerostomia in Patients Treated with Botulinum Toxin Type B for Cervical Dystonia: Observations on the Quality of Life of Patients with Xerostomia. Curr Ther Res Clin Exp. 2004; 65: pp. 161-171
  99. 99. Holmes J.M., Beck R.W., Kip K.E., Droste P.J., and Leske D.A.: Botulinum toxin treatment versus conservative management in the acute traumatic sixth nerve palsy or paresis. J AAPOS 2000; 4: pp. 145-149
  100. 100. Huang W., Foster J.A., and Rogachefsky A.S.: Pharmacology of botulinum toxin. J Am Acad Dermatol 2000; 43: pp. 249-259
  101. 101. Stefan K.A., and Konstantinovic V.S.: The therapeutic use of botulinum toxin in cervical and maxillofacial conditions: an evidence-based review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007; 104: pp. e1-e11
  102. 102. Ing E.B., Sullivan T.J., Clarke M.P., and Buncic J.R.: Oculomotor nerve palsies in children. J Pediatr Ophthalmol Strabismus 1992; 29: pp. 331-336
  103. 103. Isaac A.M.: Unilateral temporalis muscle hypertrophy managed with botulinum toxin type A. Br J Oral Maxillofac Surg 2000; 38: pp. 571-572
  104. 104. Ivanhoe C.B., Lai J.M., and Francisco G.E.: Bruxism after brain injury: successful treatment with botulinum toxin- A. Arch Phys Med Rehabil 1997; 78: pp. 1272-1273
  105. 105. Jankovic J., and Orman J.: Botulinum A toxin for cranial–cervical dystonia: a double-blind, placebo-controlled study. Neurology 1987; 37: pp. 616-623
  106. 106. Jongerius P.H., Van Den Hoogen F., Van Limbeek J., Gabreëls F.J., Van Hulst K., and Rotteveel J.J.: Effect of botulinum toxin in the treatment of drooling: a controlled clinical trial. Pediatrics 2004; 114: pp. 620-627
  107. 107. Jost Wh , Blumel J., and Grafe S.: Botulinum neurotoxin type A free of complexing proteins (XEOMIN) in focal dystonia. Drugs 2007; 67: pp. 669-683
  108. 108. Kane M.A.: Nonsurgical treatment of platysmal bands with injection of botulinum toxin A. Plast Reconstr Surg 1999; 103: pp. 656-663
  109. 109. Kerr N.C., and Hoehn M.B.: Botulinum toxin for sixth nerve palsies in children with brain tumors. J AAPOS 2001; 5: pp. 21-25
  110. 110. Krohel G.B., Cipollo C.I., and Gadipatti K.: Contralateral botulinum toxin injections improve drinking ability and facial symmetry in patients with facial paralysis. Am J Ophthalmol 2005; 135: pp. 540
  111. 111. Laccourreye O., Muscatelo L., and Naude C.: Botulinum toxin type A for Frey’s syndrome: a preliminary prospective study. Ann Otol Rhinol Laryngol 1998; 107: pp. 52-55
  112. 112. Lagalla G., Millevolte M., Capecci M., Provinciali L., and Ceravolo M.G.: Botulinum toxin type A for drooling in Parkinson’s disease: a double-blind, randomized, placebo-controlled study. Mov Disord 2006; 21: pp. 121-125
  113. 113. Lamanna C.: The most poisonous poison. Science 1959; 130: pp. 763-772
  114. 114. Lang A.M.: Botulinum toxin type A therapy in chronic pain disorders. Arch Phys Med Rehabil 2003; 84: pp. S69-73
  115. 115. Larheim Ta , Westesson Pl , and Sano T.: Temporomandibular joint disk displacement: comparison in asymptomatic volunteers and patients. Radiology 2001; 218: pp. 428-432
  116. 116. Laskawi R., Drobik C., and Schonebeck C.: Up-to-date report of botulinum toxin type A treatment in patients with gustatory sweating (Frey’s syndrome). Laryngoscope 1998; 108: pp. 381-384
  117. 117. Laskawi R., Rohrbach S., Rödel R., and Surgical : Nonsurgical Treatment Options in Patients With Movement Disorders of the Platysma. J Oral Maxillofac Surg 2002; 60: pp. 157-162
  118. 118. Lew M.F., Adornato B.T., and Duane D.D.: Botulinum toxin type B: A double-blind, placebo-controlled, safety and efficacy study in cervical dystonia. Neurology 1997; 49: pp. 701-707
  119. 119. Lew M.F., Brashear A., and Factor S.: The safety and efficacy of botulinum toxin type B in the treatment of patients with cervical dystonia: Summary of three controlled clinical trials. Neurology 2000; 55: pp. S29-S35
  120. 120. Lger G., Anthoy E., and Brisse T.: Botulinum toxin to improve facial wound healing: a prospective, blinded, placebo-controlled study. Mayo Clin Proc 2006; 81: pp. 1023-1028
  121. 121. L TJ, S GL, C LB. Special forms of strabismus. In: S JW, B EG, D AV, et al, (eds.) Pediatric Ophthalmology and Strabismus. San Francisco (CA): American Academy of Ophthalmology; 2004–2005. p. 140–41.
  122. 122. Lipp A., Trottenberg T., Schink T., Kupsch A., and Arnold G.: A randomized trial of botulinum toxin A for treatment of drooling. Neurology 2003; 61: pp. 1279-1281
  123. 123. Lovely F.W., and Copeland R.A.: Reduction eminoplasty for chronic recurrent luxation of the temporomandibular joint. J Can Dent Assoc 1981; 3: pp. 179-184
  124. 124. Lowe N.J., Maxwell A., and Harper H.: Botulinum A exotoxin for glabellar folds: A double-blind, placebo-controlled study with an electromyographic injection technique. J Am Acad Dermatol 1996; 35: pp. 569-572
  125. 125. Lowe N.J., Yamauchi P.S., Lask G.P., Patnaik R., and Moore D.: Botulinum toxins types A and B for brow furrows: Preliminary experiences with type B toxin dosing. J Cosmet Laser Ther 2002; 4: pp. 15-18
  126. 126. Lowe P., Patnaik R., and Lowe N.: Comparison of two formulations of botulinum toxin type A for the treatment of glabellar lines: A double-blind, randomized study. J Am Acad Dermatol 2006; 55: pp. 975-980
  127. 127. Lowe P.L., Patnaik R., and Lowe N.J.: A comparison of two botulinum type A toxin preparations for the treatment of glabellar lines: Double-blind, randomized, pilot study. Dermatol Surg 2005; 31: pp. 1651-1654
  128. 128. Lundh H., and Westesson P.L.: Clinical signs of temporomandibular joint internal derangement in adults. An epidemiologic study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1991; 72: pp. 637-641
  129. 129. Mancini F., Zangaglia R., Cristina S., Sommaruga M.G., Martignoni E., Nappi G., and Pacchetti C.: Double-blind, placebo-controlled study to evaluate the efficacy and safety of botulinum toxin type A in the treatment of drooling in parkinsonism. Mov Disord 2003; 18: pp. 685-688
  130. 130. Marchese-Ragona R., De Filippis C., and Staffieri A.: Parotid gland fistula: treatment with botulinum toxin. Plast Reconstr Surg 2001; 107: pp. 886-887
  131. 131. Marchese-Ragona R., Galzignato P.F., and Marioni G.: Endoscopic diagnosis of rhino-parotid fistula and successful treatment with botulinum toxin. Laryngoscope 2005; 115: pp. 2062-2064
  132. 132. Marchese-Ragona R., Marioni G., and Restivo A.D.: The role of botulinum toxin in postparotidectomy fistula treatment. A technical note. Am J Otolaryngol 2006; 27: pp. 221-224
  133. 133. M S, V M, P T, K V. Botulinum toxin in the treatment of sialorrhea. Abstracts Toxins/Toxicon 2008; 51: 50.
  134. 134. Matarasso A., Matarasso S.L., and Brandt F.S.: Botulinum A exotoxin for the management of platysma bands. Plast Reconstr Surg 1999; 103: pp. 645-652
  135. 135. Matarasso S.L.: Comparison of botulinum toxin types A and B: A bilateral and double-blind randomized evaluation in the treatment of canthal rhytides. Dermatol Surg 2003; 29: pp. 7-13
  136. 136. Mazow M.L.: Third cranial nerve palsy: Diagnosis and management strategies. In Rosenbaum A.L., and Santiago A.P. (eds): Clinical Strabismus Management: Principles and Surgical Technique. Philadelphia (PA): W.B. Saunders, 1999. pp. 251-258
  137. 137. Mckellar G., and Lorentz I.: The use of botulinum-toxin in the treatment of oromandibular dystonias and fractures of the mandibular condyle. Aust N Z J Med 1992; 22: pp. 428
  138. 138. Metai M.: Morphological and functional-changes in masseter after administration of botulinum toxin for treatment of masseteric hypertrophy. J Dent Res 1996 May; 75: pp. 1164
  139. 139. Metz H.S., and Mazow M.: Botulinum toxin treatment of acute sixth and third nerve palsy. Graefes Arch Clin Exp Ophthalmol 1988; 226: pp. 141-144
  140. 140. Middlebrook J.L., and Franz D.R.: Botulinum toxins. In Sidell F.R., Takafuji E.T., and Franz D.R. (eds): Textbook of Military Medicine, Part I: Warfare, Weaponry, and the Casualty—Medical Aspects of Chemical and Biological Warfare. Washington, DC: Department of the Army, Office of The Surgeon General, Borden Institute, 1997. pp. 643-654
  141. 141. Miller S.C., and Firestone J.M.: Psychosomatic factors in the aetiology of periodontal diseases. Am J Orthodont Oral Surg 1947; 33: pp. 675-680
  142. 142. Montoya F.J., Riddell C.E., Caesar R., and Hague S.: Treatment of gustatory hyperlacrimation (crocodile tears) with injection of botulinum toxin into the lacrimal gland. Eye 2002; 16: pp. 705-709
  143. 143. Moore A.P., and Wood C.G.: Medical treatment of recurrent temporomandibular joint dislocation using botulinum toxin A. Br Dent J 1997; 183: pp. 415-417
  144. 144. Moore A.P., and Wood G.D.: The Medical Management of Masseteric Hypertrophy With Botulinum Toxin Type A. Br J Oral Maxillofac Surg 1994; 32: pp. 26-28
  145. 145. Moreau M.S., Cauhepe C., Magues J.P., and Senard J.M.: A double-blind, randomized, comparative study of Dysport vs. BOTOX in primary palmar hyperhidrosis. Br J Dermatol 2003; 149: pp. 1041-1045
  146. 146. Niamtu J., and Campbell R.L.: The anesthetic skin patch for topical cutaneous anesthesia. J Oral Maxillofac Surg 1984; 42: pp. 839-840
  147. 147. Niamtu J.: Aesthetic uses of botulinum toxin A. J Oral Maxillofac Surg 1999; 57: pp. 1228-1233
  148. 148. Niamtu J.: Botulinum Toxin A: A Review of 1,085 Oral and Maxillofacial Patient Treatments. J Oral Maxillofac Surg 2003; 61: pp. 317-324
  149. 149. Niamtu J.: Cosmetic facial surgery. Oral Maxillofac Surg Clin North Am 2000; 12: pp. 595
  150. 150. O’day J.: Use of botulinum toxin in neuro-opthalmology. Curr Opin Opthalmol 2001; 12: pp. 419-422
  151. 151. Ohishi I.: Oral toxicities of . Infect Immun. 1984; 43: pp. 487-490
  152. 152. Okeson J.P.: Orofacial Pain: Guidelines for Assessment, Diagnosis and Management. Chicago: Quintessence Co., 1996.
  153. 153. Ondo W.G., Hunter C., and Moore W.: A double-blind placebocontrolled trial of botulinum toxin B for sialorrhea in Parkinson’s disease. Neurology 2004; 62: pp. 37-40
  154. 154. Padberg M., De Bruijn S.F., De Haan R.J., and Tavy D.L.: Treatment of chronic tension-type headache with botulinum toxin: a doubleblind, placebo-controlled clinical trial. Cephalalgia 2004; 24: pp. 675-680
  155. 155. Pal P.K., Calne D.B., Calne S., and Tsui J.K.: Botulinum toxin A as treatment for drooling saliva in PD. Neurology 2000; 54: pp. 244-247
  156. 156. Pappert E., Leong M., and Royal M.: Botulinum toxin type B compared with type A in the treatment of patients with cervical dystonia: results from a randomized, double-blind non-inferiority study. Neurology 2006; 66: pp. A252
  157. 157. Park Y.C., Lim J.K., Lee D.K., and Yi S.D.: Botulinum a toxin treatment of hemifacial spasm and blepharospasm. J Korean Med Sci 1993; 8: pp. 334-340
  158. 158. Pérez D.M., and Espiga P.G.: Recurrent Temporomandibular Joint Dislocation Treated With Botulinum Toxin: Report of 3 Cases. J Oral Maxillofac Surg 2004; 62: pp. 244-246
  159. 159. Poewe W., Deuschl G., Nebe A., Feifel E., Wissel J., and Benecke R.: What is the optimal dose of botulinum toxin A in the treatment of cervical dystonia? Results of a double blind, placebo controlled, dose ranging study using Dysport. German Dystonia Study Group. J Neurol Neurosurg Psychiatry 1998; 64: pp. 13-17
  160. 160. Porta M., Gamba M., and Bertacci G.: Treatment of sialorrhea with ultrasound guided botulinum toxin type A injections in patients with neurological disorders. J Neurol Neurosurg Psychiatry 2001; 70: pp. 538-540
  161. 161. Quah B.L., Ling Y.L., Cheong P.Y., and Balakrishnan V.: A review of 5 years’ experience in the use of botulinium toxin A in the treatment of sixth cranial nerve palsy at the Singapore National Eye Centre. Singapore Med J 1999; 40: pp. 405-409
  162. 162. Racette B.A., Good L., Sagitto S., and Perlmutter J.S.: Botulinum toxin B reduces sialorrhea in Parkinsonism. Mov Disrod 2003; 18: pp. 1059-1061
  163. 163. Ramirez A.L., Reeck J., and Maas C.S.: Botulinum toxin type B (MyoBloc) in the management of hyperkinetic facial lines. Otolaryngol Head Neck Surg 2002; 126: pp. 459-467
  164. 164. R OM, M GF, M A. The extended subperiosteal face lift: a definitive soft-tissue remodeling for facial rejuvenation. Plast Reconstr Surg 88:227–36, discussion 1991; 237–8.
  165. 165. Redding G.R., Rubright W.C., and Zimmerman S.O.: Incidence of brnxism. J Dent Res 1966; 45: pp. 1198-1204
  166. 166. Relja M., and Telarovic S.: Botulinum toxin in tension-type headache. J Neurol 2004; 251: pp. I12-I14
  167. 167. Restivo D.A., Lanza S., and Patti F.: Improvement of diabetic autonomic gustatory sweating by botulinum toxin type A. Neurology 2002; 59: pp. 1971-1973
  168. 168. Rieder C.R., Schestatsky P., Socal M.P., Monte T.L., Fricke D., and Costa J.: A double-blind, randomized, crossover study of prosigne versus botox in patients with blepharospasm and hemifacial spasm. Clin Neuropharmacol 2007; 30: pp. 39-42
  169. 169. Riemann R., Pfennigsdorf S., and Riemann E.: Successful treatment of crocodile tears by injection of botulinum toxin into the lacrimal gland: a case report. Ophthalmology 1999; 106: pp. 2322-2324
  170. 170. Rijsdijk B.A.: Botulinum toxin Type A treatment of cosmetically disturbing masseteric hypertrophy (DUT). Ned Tijdschr Geneeskd 1998; 142: pp. 529-532
  171. 171. Rollnik J.D., Tanneberger O., Schubert M., Schneider U., and Dengler R.: Treatment of tension-type headache with botulinum toxin type A: A double-blind, placebo-controlled study. Headache 2000; 40: pp. 300-305
  172. 172. Rowe N.L., and Williams L.I.: Fracture of the zygomatic complex and orbit. In (eds): , 2nd edition. Churchill Livingstone, 1994. pp. 515
  173. 173. Saad N., and Lee J.: The role of botulinum toxin in third nerve palsy. Aust N Z J Ophthalmol 1992; 20: pp. 121-127
  174. 174. Sadick N.: Prospective open-label study of botulinum toxin type B (Myobloc) at doses of 2,400 and 3,000 U for the treatment of glabellar wrinkles. Dermatol Surg 2003; 29: pp. 501-507
  175. 175. Sadick N.S.: Botulinum toxin type B for glabellar wrinkles: A prospective open-label response study. Dermatol Surg 2002; 28: pp. 817-821
  176. 176. Sadick N.S., and Matarasso S.L.: Comparison of botulinum toxins A and B in the treatment of facial rhytides. Dermatol Clin 2004; 22: pp. 221-226
  177. 177. Sadiq S.A., and Downes R.N.: A clinical algorithm for the management of facial nerve palsy from an oculoplastic perspective. Eye 1998; 12: pp. 219-223
  178. 178. Said S.Z., Meshkinpour A., Carruthers A., and Carruthers J.: Botulinum toxin A: its expanding role in dermatology and esthetics. Am J Clin Dermatol 2003; 4: pp. 609-616
  179. 179. Savarese R., Diamond M., Elovic E., and Millis S.R.: Intraparotid injection of botulinum toxin A as a treatment to control sialorrhea in children with cerebral palsy. Am J Phys Med Rehabil 2004; 83: pp. 304-311
  180. 180. Schantz E.J., and Johnson E.A.: Properties and use of botulinum toxin and other microbial neurotoxins in medicine. Microbiol Rev. 1992; 56: pp. 80-99
  181. 181. Schmitt W.J., Slowey E., Fravi N., Weber S., and Burgunder J.M.: Effect of botulinum toxin A injections in the treatment of chronic tension-type headache: a double-blind, placebo-controlled trial. Headache 2001; 41: pp. 658-664
  182. 182. Schneider S.A., Aggarwal A., Bhatt M., Dupont E., Tisch S., and Limousin P.: Severe tongue protrusion dystonia — clinical syndromes and possible treatment. Neurology 2006; 67: pp. 940-943
  183. 183. Schulte-Mattler W.J., and Krack P.: Treatment of chronic tension-type headache with botulinum toxin A: a randomized, double-blind, placebo-controlled multicenter study. Pain 2004; 109: pp. 110-114
  184. 184. Schulte-Mattler W.J., Wieser T., and Zierz S.: Treatment of tensiontype headache with botulinum toxin: a pilot study. Eur J Med Res 1999; 4: pp. 183-186
  185. 185. Schwaag S., Vollmer-Haase J., Rahman A., Frese A., Husstedt Iw , and Evers S.: Botulinum toxin A in the prophylactic treatment of migraine—a randomized, double-blind, placebo-controlled study. Cephalalgia 2004; 24: pp. 838-843
  186. 186. Scott A.B.: Botulinum toxin injection of eye muscles to correct strabismus. Trans Am Ophthalmol Soc 1981; 79: pp. 734-770
  187. 187. Scott A.B., Rosenbaum A., and Collins C.C.: Pharmacologic weakening of extraocular muscles. Invest Ophthalmol 1973; 12: pp. 924-927
  188. 188. Scott A.B., and Suzuki D.: Systemic toxicity of botulinum toxin by intramuscular injection in the monkey. Mov Disord. 1988; 3: pp. 333-335
  189. 189. Scott K.R., Kothari M.J., Venkatesh Y.S., Murphy T., and Simmons Z.: Parotid gland injections of botulinum toxin A are effective in treating sialorrhea in amyotrophic lateral sclerosis. J Clin Neuromuscul Dis 2005; 7: pp. 62-65
  190. 190. Sen P., and Papesch M.: Botulinum Toxin A for the Management of Gustatory Sweating. Otolaryngol Head and Neck Surg 2008; 139: pp. 126
  191. 191. Senno R.G., Marciniak C.M., Olsson A.B., Esposito N., and Duraski S.A.: Botulinum Toxin Type A in the Treatment of Temporomandibular Joint Dislocation in an Adult With Anoxic Brain Injury: A Case Report. (Abstract). Arch Phys Med Rehabil 2003; 84: pp. E8
  192. 192. Sessle B.J.: Neural mechanisms and neuroplasticity related to deep craniofacial pain. Pain Forum 1997; 6: pp. 173-175
  193. 193. Shaari C.M.: Quantifying the spread of botulinum toxin through muscle fascia. Laryngoscope 1991; 101: pp. 960-963
  194. 194. Shaari C.M., Bei-Lian W.U., Biller H.F., Chuang S.-K., and Sanders I.: Botulinum toxin decreases the salivation from canine submandibular glands. Otolaryngol Head Neck Surg 1998; 118: pp. 452-457
  195. 195. Shorey C.W., and Campbell J.H.: Dislocation of the temporomandibular joint (Review). Oral Med Oral Pathol Oral Radiol Endod 2000; 89: pp. 662-668
  196. 196. Silberstein S., Mathew N., Saper J., and Jenkins S.: Botulinum toxin type A as a migraine preventive treatment. Headache 2000; 40: pp. 445-450
  197. 197. Smet-Dieleman H., Van De Heyning P.H., and Tassignon M.J.: Botulinum A toxin injection in patients with facial nerve palsy. Acta Otorhinolaryngol Belg 1993; 47: pp. 359-363
  198. 198. Smith H.S., Audette J., and Royal M.A.: Botulinum toxin in pain management of soft tissue syndromes. Clin J Pain 2002; 18: pp. S147-S154
  199. 199. Smith L.D.S.: The occurrence of . Health Lab Sci. 1978; 15: pp. 74-80
  200. 200. Sobel J., Tucker N., and Sulka A.: Foodborne botulism in the United States, 1900–2000. Emerg Infect Dis. 2004; 10: pp. 1606-1611
  201. 201. Song P.C., Schwartz J., and Blitzer A.: The emerging role of botulinum toxin in the treatment of temporomandibular disorders. Oral Dis 2007; 13: pp. 253-260
  202. 202. Spillane K.S., Shelton J.E., and Hasty M.F.: Stroke-induced trismus in a pediatric patient: Long-term resolution with botulinum toxin A. Am J Phys Med Rehabil 2003; 82: pp. 485-488
  203. 203. Stell R., Coleman R., Thompson P., and Marsden C.D.: Botulinum toxin treatment of spasmodic torticollis. BMJ 1988; 297: pp. 616
  204. 204. Stern R.S.: Clinical practice. Treatment of photoaging. N Engl J Med 2004; 350: pp. 1526-1534
  205. 205. Stip E., Faughnan M., Desjardin I., and Labrecque R.: Botulinum toxin in a case of severe tardive dyskinesia mixed with dystonia. Br J Psychiatry 1992; 161: pp. 867-868
  206. 206. Sugiyama H.: [object Object]. Microbiol Rev. 1980; 44: pp. 419-448
  207. 207. Suskind D.L., and Tilton A.: Clinical study of botulinum-A toxin in the treatment of sialorrhea in children with cerebral palsy. Laryngoscope 2002; 112: pp. 73-81
  208. 208. Svenson P.: Pain mechanisms in myogenous temporomandibular disorders. Pain Forum 1997; 6: pp. 158-165
  209. 209. Talarico-Filho S., Mendonça D.O., Nascimento M., Sperandeo D.E., Macedo F., and Sanctis D.E.: A double-blind, randomized, comparative study of two type A botulinum toxins in the treatment of primary Axillary hyperhidrosis. Dermatol Surg 2007; 33: pp. S44-S50
  210. 210. Talebnejad M.R., Sharifi M., and Nowroozzadeh M.H.: The role of Botulinum toxin in management of acute traumatic third-nerve palsy. J AAPOS 2008; 12: pp. 510-513
  211. 211. Tan E.K., Fook-Chong S., Lum S.Y., and Lim E.: Botulinum toxin improves quality of life in hemifacial spasm: validation of a questionnaire (HFS-30). J Neurol Sci 2004; 219: pp. 151-155
  212. 212. Tan E.K., and Jankovic J.: Treating severe bruxism with botulinum toxin. J Am Dent Assoc 2000; 131: pp. 211-216
  213. 213. Tan E.K., and Jankovic J.: Botulinum toxin A in patients with oromandibular dystonia: long-term follow-up. Neurology 1999; 53: pp. 2102-2107
  214. 214. Tan E.K., Lo Y.L., Seah A., and Auchus A.P.: Recurrent jaw dislocation after botulinum toxin treatment for sialorrhoea in amyotrophic lateral sclerosis. J Neurol Sci 2001; 190: pp. 95-97
  215. 215. Tang X., and Wan X.: Comparison of Botox with a Chinese type A botulinum toxin. Chin Med J (Engl) 2000; 113: pp. 794-798
  216. 216. Ting P.T., and Freiman A.: The story of . Clin Med 2004; 4: pp. 258-261
  217. 217. Titner R., and Jankovic J.: Botulinum toxin type A in the management of oromandibular dystonia and bruxism. In Brin M.F., Hallet M., and Jankovic J. (eds): Scientific and therapeutic aspects of botulinum toxin. Philadelphia: Lippincott: Williams and Wilkins, 2002. pp. 343-356
  218. 218. Tokuno T., Nakazawa K., Yoshida S., Matsumoto S., Shingu T., and Sato S.: Primary oculomotor nerve palsy due to head injury: analysis of 10 cases. No Shinkei Geka 1995; 23: pp. 497-501
  219. 219. Truong D.D., Hermanowicz N., and Rontal M.: Botulinum toxin in treatment of tardive dyskinetic syndrome. J Clin Psychopharmacol 1990; 10: pp. 438-439
  220. 220. Truong D.D., and Jost W.H.: Botulinum toxin: Clinical use (Review). Parkinsonism and Related Disorders 2006; 12: pp. 331-355
  221. 221. Van Zandijcke M., and Marchau M.M.: Treatment of bruxism with botulinum toxin injections. J Neurol Neurosurg Psychiatry 1990; 53: pp. 530
  222. 222. Vargas H., Galatti L.T., and Parnes S.M.: A pilot study evaluationing the treatment of postparotidectomy sialoceles with botulinum toxin type A. Arch Otolaryngol Head Neck Surg 2000; 126: pp. 421-424
  223. 223. Varma J.K., and Katsitadze G.: Moiscrafishvili. Signs and symptoms predictive of death in patients with foodborne botulism—Republic of Georgia, 1980–2002. Clin Infect Dis. 2004; 39: pp. 357-362
  224. 224. Verma A., and Steele J.: Botulinum toxin improves sialorrhea and quality of living in bulbaramyotrophic lateral sclerosis. Muscle Nerve 2006; 34: pp. 235-237
  225. 225. Von Lindern J.J., Niederhagen B., Berge S., and Appel T.: Type A botulinum toxin in the treatment of chronic facial pain associated with masticatory hyperactivity. J Oral Maxillofac Surg 2003; 61: pp. 774-778
  226. 226. Watanabe Y., Bakheit A., and Mclellan D.: A study of the effectiveness of botulinum toxin type A (Dysport) in the management of muscle spasticity. Disabil Rehabil: Int Multidiscip J 1998; 20: pp. 62-65
  227. 227. Widmer C.G.: Idiopathic masticatory muscle pain. Pain Forum 1997; 6: pp. 170-172
  228. 228. Winterholler M.G., Erbguth F.J., Wolf S., and Kat S.: Botulinum toxin for the treatment of sialorrhoea in ALS: serious side effects of a transductal approach [comment]. J Neurol Neurosurg Psychiatry 2001; 70: pp. 417-418
  229. 229. Wohlfarth K., Muller C., Sassin I., Comes G., and Grafe S.: Neurophysiological double-blind trial of a botulinum neurotoxin type a free of complexing proteins. Clin Neuropharmacol 2007; 30: pp. 86-94
  230. 230. Yao C.-C., Chao C.-H., and Hong Y.-K.: Novel action of botulinum toxin on the stromal and epithelial components of the prostate gland. J Urol 2006; 175: pp. 1158-1163
  231. 231. Yasufuku-Takano J., Sakurai M., Kanazawa I., and Nagaoka M.: Successful treatment of intractable tardive dyskinesia with botulinum toxin. J Neurol Neurosurg Psychiatry 1995; 58: pp. 511-512
  232. 232. Yoshimura D.M., Aminoff M.J., Tami T.A., and Scott A.B.: Treatment of hemifacial spasm with botulinum toxin. Muscle Nerve 1992; 15: pp. 1045-1049
  233. 233. Zhibo X., and Miaobo Z.: Botulinum toxin type A affects cell cycle distribution of fibroblasts derived from hypertrophic scar. J Plast Reconstr Aesthet Surg 2008; 61: pp. 1128-1129
  234. 234. Zhibo X., and Miaobo Z.: Potential therapeutical effects of botulinum toxin type A in keloid management. Medical Hypotheses 2008; 71: pp. 623
  235. 235. Ziegler C.M., Haag C., and Mühling J.: Treatment of recurrent temporomandibular joint dislocation with intramuscular botulinum toxin injections. Clin Oral Invest 2003; 7: pp. 52-55
  236. 236. Zwart J.A., Bovim G., Sand T., and Sjaastad O.: Tension headache: botulinum toxin paralysis of temporal muscles. Headache 1994; 34: pp. 458-462
Only gold members can continue reading. Log In or Register to continue

Related posts:

  1. Prognosis for craniofacial fibrous dysplasia after incomplete resection: age and serum alkaline phosphatase
  2. Incidence of venous thromboembolism in oral and maxillofacial surgery: a retrospective analysis
  3. Distribution of Small Integrin-Binding LIgand, N-linked Glycoproteins (SIBLING) in the condylar cartilage of rat mandible
  4. Intraoral vertical ramus osteotomy: a simple method to prevent medial trapping of the proximal fragment
  5. Reply to a letter to the editor regarding article “Traumatic neuroma of mental nerve following chin augmentation”
  6. Mandibular osteoblastic metastasis of poorly differentiated carcinoma of the thyroid gland

Stay updated, free dental videos. Join our Telegram channel
Tags:
Feb 8, 2018 | Posted by in Oral and Maxillofacial Surgery | Comments Off on Clinical use of botulinum toxins in oral and maxillofacial surgery

VIDEdental - Online dental courses
Get VIDEdental app for watching clinical videos